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A preparation method of purpurin 18-liposome nanovesicles and its application in the preparation of drugs for treating tumors

A nanovesicle, violetin technology, applied in the directions of antitumor drugs, liposome delivery, drug delivery, etc., can solve the problems of affecting the therapeutic effect of PDT, poor solubility of violetin, and difficulty in uptake, etc., and improve passive targeting performance. , High light-to-heat conversion efficiency, and the effect of enhancing the penetration and retention effect

Active Publication Date: 2021-09-24
SHAANXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

PDT treatment uses local light to treat tumors. However, due to the strong hydrophobicity of Pp18, purpurin has poor solubility in the body, is difficult to absorb, and has low efficiency in reaching the tumor site, thus affecting the effect of PDT treatment.

Method used

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  • A preparation method of purpurin 18-liposome nanovesicles and its application in the preparation of drugs for treating tumors
  • A preparation method of purpurin 18-liposome nanovesicles and its application in the preparation of drugs for treating tumors
  • A preparation method of purpurin 18-liposome nanovesicles and its application in the preparation of drugs for treating tumors

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Experimental program
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Effect test

Embodiment 1

[0068] The synthesis of embodiment 1 purpurin 18-phospholipid

[0069] Weigh Pp18: 56.4mg, P-lyso PC: 98.7mg, EDCI: 38.35mg, DMAP: 24.35mg, dissolve in 10mL of anhydrous chloroform, add in sequence to the reaction bottle filled with argon, and stir at room temperature in the dark After 24 hours, the reaction was completed. Mix the reaction mixture with silica gel powder, evaporate the solvent to dryness at 37°C, and purify using silica gel column chromatography with gradient elution. The ratio is 9:1, ② chloroform: methanol volume ratio is 8.5: 1.5, ③ chloroform: methanol: acetic acid volume ratio is 8: 1.5: 0.5, collect Pp18-lipid, use a rotary evaporator to initially evaporate the solvent, Blow dry with nitrogen, dry in vacuum for 3 h, and store in -20°C refrigerator.

Embodiment 2

[0070] The synthesis of embodiment 2 purpurin 18-phospholipids

[0071] Weigh Pp18: 112.8mg, P-lyso PC: 98.7mg, EDCI: 38.35mg, DMAP: 24.35mg, dissolve in 10mL of anhydrous chloroform, add to the reaction bottle filled with argon in turn, and stir at room temperature in the dark After 24 hours, the reaction was completed. Mix the reaction mixture with silica gel powder, evaporate the solvent to dryness at 37°C, and purify using silica gel column chromatography with gradient elution. The ratio is 9:1, ② chloroform: methanol volume ratio is 8.5: 1.5, ③ chloroform: methanol: acetic acid volume ratio is 8: 1.5: 0.5, collect Pp18-lipid, use a rotary evaporator to initially evaporate the solvent, Blow dry with nitrogen, dry in vacuum for 3 h, and store in -20°C refrigerator.

Embodiment 3

[0072] The synthesis of embodiment 3 purpurin 18-phospholipids

[0073] Weigh Pp18: 112.8mg, P-lyso PC: 98.7mg, EDCI: 76.7mg, DMAP: 48.7mg, dissolve in 10mL of anhydrous chloroform, add in sequence to a reaction bottle filled with argon, and stir at room temperature in the dark After 24 hours, the reaction was completed, the reaction mixture was mixed with silica gel powder, the solvent was evaporated to dryness, and the solvent was purified by silica gel column chromatography, gradient elution, and the polarity of the eluent was in order from high to low. 9:1, ② chloroform: methanol volume ratio is 8.5: 1.5, ③ chloroform: methanol: acetic acid volume ratio is 8: 1.5: 0.5, collect Pp18-lipid, use rotary evaporator to preliminarily evaporate the solvent to dryness, nitrogen blow Dry, vacuum-dry for 3 hours, and store in a -20°C refrigerator.

[0074] By changing the ratio of the reactants Pp18, P-lyso PC and the two catalysts (both EDCI and DMAP are catalysts), when the molar ...

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Abstract

A method for preparing purpurin 18-liposome nanovesicles and its application in the preparation of drugs for treating tumors, using organic acylation to combine purpurin 18 with 1-palmitoyl-2-hydroxyl-sn-glycerol- 3-Phosphocholine is covalently linked to construct a Pp18-lipid covalent conjugate, and the Pp18-lipid covalent conjugate, distearoylphosphatidylcholine, cholesterol, distearoylphosphatidylethanolamine-polyethylene glycol 2000 Mixing, film forming, hydration, extrusion. The present invention improves the loading rate of purpurin 18 on liposomes; improves the water solubility of Pp18, can independently control the loading efficiency of Pp18, and makes liposomes with a particle size of about 100nm, synergizing its effect on tumor sites Osmotic retention effect, improve drug utilization and PDT treatment effect, and use high proportion of Pp18-lipid good photothermal conversion performance, can be used for PTT treatment of tumors.

Description

technical field [0001] The invention belongs to the field of nano-pharmaceutical preparations, and relates to a method for preparing purpurin 18-liposome nanovesicles and its application in preparing drugs for treating tumors. Background technique [0002] As one of the largest public health problems in the world, malignant tumors have greatly endangered human health and become the number one killer of human beings in the new century. Current tumor treatment strategies mainly include surgery, drug therapy, radiotherapy and biological therapy, each of which has certain drawbacks: surgical treatment is risky, prone to recurrence and metastasis; drug treatment, due to its non-tumor targeting, can cause severe Toxic and side effects; high cost of biological treatment, easy to relapse; long radiation therapy cycle, there is radiation damage. Among them, photodynamic therapy (PDT) and photothermal therapy (PTT) produced by near-infrared laser irradiation can remove tumor tissue a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/54A61K41/00A61P35/00
CPCA61K41/0071A61K47/544A61K47/6911A61P35/00
Inventor 王筱冰高晔王攀刘全宏张坤
Owner SHAANXI NORMAL UNIV
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