Pegylated celastrol and preparation method and application thereof

A technology of triptolide and pegylation, which is applied in the field of medicine, can solve the problems of no triptolide drug, high toxicity, and marketing, and achieves the effect of prolonging the elimination half-life, reducing the toxic and side effects, and reducing the frequency of administration. Effect

Inactive Publication Date: 2012-11-28
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, due to the disadvantages of poor water solubility and...

Method used

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  • Pegylated celastrol and preparation method and application thereof
  • Pegylated celastrol and preparation method and application thereof
  • Pegylated celastrol and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1: mPEG 10k - Preparation of NHCO-Celastrol

[0040] Tripterine 4.5 g (10 mmol) was added with DCC 2.06 g (10 mmol), DMAP 0.5 g (4 mmol), TEA 550 μg (5.45 mmol) and methoxyaminopolyethylene glycol 10 kDa (mPEG 10k -CH 2 CH 2 -NH 2 HCl) in 50 g (4.76 mmol) of anhydrous dichloromethane solution, react at room temperature, and monitor the reaction process by spotting on a silica gel plate. After the reaction is complete, filter the reaction solution, evaporate the filtrate to dryness, add deionized water, extract with dichloromethane, dry the organic phase with anhydrous sodium sulfate, concentrate, and precipitate with cold ether. Multiple washes to obtain mPEG 10k -NHCO-Celastrol product 52.13 g, is a red-yellow solid, and its modification rate was determined by HPLC-UV.

[0041] mPEG 10k -NHCO-Celastrol has a molecular weight of 10981.5 (MALDI-TOF-TOF).

Embodiment 2

[0042] Example 2: mPEG 10k - Preparation of NHCO-Celastrol

[0043] 0 ℃ filled with N 2 Under the conditions of chloroformate, 0.642 g (4.7 mmol) of isobutyl chloroformate was added to anhydrous dichloromethane solution containing 4.5 g (10 mmol) of tripterine (10 mmol) and 1.5 g (15.15 mmol) of NMP, and the reaction was carried out for 20 min, followed by the addition of mPEG pre-supplemented with TEA 550 μg (5.45 mmol) 10k -CH 2 CH 2 -NH 2 50 g (4.76 mmol) of HCl in dichloromethane solution, kept at 0 °C for 2 h, moved to room temperature to continue the reaction, and monitored the reaction progress by spotting on a silica gel plate. After the reaction is complete, filter the reaction solution, evaporate the filtrate to dryness, add deionized water, extract with dichloromethane, dry the organic phase with anhydrous sodium sulfate, concentrate, and precipitate with cold ether. Multiple washes to obtain mPEG 10k -NHCO-Celastrol product 51.65 g, is a reddish-yellow...

Embodiment 3

[0044] Example 3: mPEG 10k - Preparation of NHCO-Celastrol

[0045] Add 4.5 g (10 mmol) of tripterine into anhydrous dichloromethane solution containing 0.863 g (7.5 mmol) of NHS and 2.06 g (10 mmol) of DCC, react at 25°C, filter, evaporate the filtrate to dryness, and obtain Tripterygium wilfordii Ruby succinimidyl ester. In addition mPEG 10k -CH 2 CH 2 -NH 2 Dissolve 50 g (4.76 mmol) of HCl in anhydrous dichloromethane solution, adjust the pH to 9.0 with TEA, add the above-mentioned tripterine succinimide ester, react at 25 °C, and monitor the reaction process by spotting on a silica gel plate. After the reaction is complete, filter the reaction solution, evaporate the filtrate to dryness, add deionized water, extract with dichloromethane, dry the organic phase with anhydrous sodium sulfate, concentrate, and precipitate with cold ether. Multiple washes to obtain mPEG 10k -NHCO-Celastrol product 52.05 g, a reddish-yellow solid, its modification rate was determine...

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Abstract

The invention belongs to the technical field of medicine, and relates to pegylated celastrol and a preparation method and application thereof. The pegylated celastrol has a structure shown as a general formula in the specifications. The invention also provides application of the pegylated celastrol and methoxy amino polyethylene glycol 10kDa mono-modified celastrol (mPEG10k-NHCO-celastrol) to preparation of medicines for treating various malignant tumors such as prostatic cancer, lung cancer, liver cancer and cervical cancer. Celastrol is subjected to chemical structural modification by PEG, so that the problem that the celastrol has low solubility can be solved; and an injection can be prepared after the celastrol is modified by the PEG, so that the elimination half life of the celastrol can be prolonged through in-vivo injection, the toxic and side effects of the celastrol are reduced, and the administration frequency of a patient is reduced.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to pegylated tripterine and its preparation method and application. Background technique [0002] Triptergium wilfordii (Triptergium wilfordii) is an annual vine of the Euonymus family. As a Chinese herbal medicine commonly used in traditional Chinese medicine, Tripterygium wilfordii has a history of more than 700 years. Clinical practice shows that it has a significant effect on autoimmune diseases, nephrotic syndrome, cancer and other diseases. Studies have found that there are three main active ingredients in Tripterygium wilfordii: triptolide, triptolide, and triptolide. Celastrol, Tripterine, abbreviation: red element, also known as celastrol, is a monomer with multiple activities in the main active ingredients of Tripterygium wilfordii. It belongs to triterpenoid pigments and is derived from the Root bark, whose molecular formula is C 29 h 38 o 4 , the relative molecular ...

Claims

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Application Information

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IPC IPC(8): C08G65/48A61K31/765A61P35/00
Inventor 孙彦华朱孔黎曹志娟梁建英刘彩云卢建忠
Owner FUDAN UNIV
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