Preparation method and application of gemcitabine-phospholipid complex

A phospholipid complex, gemcitabine technology, applied in non-active ingredients medical preparations, active ingredients-containing medical preparations, pharmaceutical formulas and other directions, can solve the problems of easy inactivation, short half-life, etc., and achieve easy absorption and reduce toxicity. , good therapeutic effect

Active Publication Date: 2018-11-02
上海云洛生物技术有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Gemcitabine is a water-soluble anti-tumor drug, which is easily inactivated in the body and has a short half-life in vivo (only 32-94 minutes), and water-soluble gemcitabine is resistant to nucleoside transporters due to the lack of nucleoside transporter

Method used

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  • Preparation method and application of gemcitabine-phospholipid complex
  • Preparation method and application of gemcitabine-phospholipid complex
  • Preparation method and application of gemcitabine-phospholipid complex

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preparation example Construction

[0020] A preparation method of gemcitabine-phospholipid complex, comprising the following specific steps: under nitrogen protection, gemcitabine, phospholipid, calcium salt, buffer and surfactant are formulated into an aqueous solution reaction system; the reaction temperature is 30-50 degrees Celsius, adding Continue mechanical stirring after phospholipase D, and the stirring time is 3-10 hours; after the reaction, add an organic solution to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by rotary evaporation, and dry in vacuum to obtain gemcitabine-phospholipid Complex.

[0021] The structural formula of the gemcitabine is

[0022]

[0023] The structural formula of the phosphatidylcholine PC is

[0024]

[0025] React under the action of phospholipase D, calcium salt to obtain gemcitabine-phospholipid complex, the structural formula of gemcitabine-phospholipid complex is

[0026]

[0027] In the formula, R1 and ...

Embodiment 1

[0030] Embodiment 1: Preparation of gemcitabine-phospholipid complex

[0031]Under the protection of nitrogen, add 300 g gemcitabine, 150 g soybean lecithin (the content of phosphatidylcholine is 50%), 15 g calcium acetate, 30 g Tween 80 (R) to 10 L 0.1mol / L pH=4.5 acetic acid – Stir well in sodium acetate buffer. The reaction temperature is 45 degrees Celsius. After adding phospholipase D, continue mechanical stirring for 6 hours; after the reaction, add 1.5 L of n-hexane: ethanol = 3:1 organic solvent to extract twice, combine the organic phases, and add anhydrous sulfuric acid Sodium-dried, the solvent was removed by rotary evaporation, and vacuum-dried to obtain 135 g of the gemcitabine-phospholipid complex.

Embodiment 2

[0032] Embodiment 2: Preparation of gemcitabine-phospholipid complex

[0033] Under nitrogen protection, 300 g of gemcitabine, 150 g of soybean phospholipids (the content of phosphatidylcholine is 50%), 15 g of calcium acetate, and 40 g of AOT were added to 10 L 0.1mol / L pH=4.5 acetic acid-sodium acetate buffer Stir in the liquid evenly. The reaction temperature is 45 degrees Celsius. After adding phospholipase D, continue mechanical stirring for 6 hours; after the reaction, add 1.5 L of n-hexane: ethanol = 3:1 organic solvent to extract twice, combine the organic phases, and add anhydrous sulfuric acid Sodium-dried, the solvent was removed by rotary evaporation, and vacuum-dried to obtain 145 g of the gemcitabine-phospholipid complex.

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Abstract

The invention relates to a preparation method of a gemcitabine-phospholipid complex. The method includes the steps of: under the protection of nitrogen, preparing gemcitabine, phospholipid, a calcium salt, a buffer solution and a surfactant into a water solution reaction system; controlling the reaction temperature at 30-50DEG C, adding phospholipase D, then carrying out continuous mechanical stirring for 3-10h; and at the end of the reaction, adding an organic solution to perform extraction twice, combining the organic phase and adding anhydrous sodium sulfate to perform drying, conducting rotary evaporation to remove the solvent, and carrying out vacuum drying so as to obtain the gemcitabine-phospholipid complex. According to the invention, through the high permeability of the phospholipid, the emcitabine-phospholipid complex transport drugs into tumor cells to increase the half-life and pharmacodynamic activity of drugs. The complex can be used for preparation of drugs treating pancreatic cancer, breast cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, lymphoma, digestive tract cancer and other malignant tumor.

Description

technical field [0001] The invention relates to a medical preparation, in particular to a preparation method and application of a gemcitabine-phospholipid complex. Background technique [0002] Gemcitabine (Gemcitabine, domestic trade name Zefei), chemical name is (+)-2'-deoxy-2',2'-difluorocytosine, is a new cytidine nucleoside derivatives, and arabinose Like cytidine, it needs to be activated by deoxycytosine kinase after entering the body to form gemcitabine phosphate, gemcitabine diphosphate and gemcitabine triphosphate, among which gemcitabine diphosphate and gemcitabine triphosphate are active substances that can inhibit DNA Synthesis, so gemcitabine is a cell cycle-specific anti-metabolite drug that mainly acts on tumor cells in the DNA synthesis phase, that is, cells in the S phase. Under certain conditions, it can prevent the progression from the G1 phase to the S phase, thereby exerting cytotoxicity. Gemcitabine can increase the stability of platinum-based chemoth...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K31/7068A61P35/00
Inventor 梁水英洪宇燕
Owner 上海云洛生物技术有限公司
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