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Multi-drug delivery retinoic acid nanoparticle solution and preparation and application thereof

A nanoparticle, retinoic acid technology, applied in the directions of drug delivery, pharmaceutical formulation, powder delivery, etc., can solve problems such as retinoic acid tolerance, and achieve the effects of clear mechanism of action, reasonable collocation, and simple preparation process

Inactive Publication Date: 2017-06-13
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

[0005] Aiming at the current problem of solid tumors being resistant to retinoic acid, the present invention provides a formulation and preparation method of retinoic acid multi-drug co-delivery nanoparticles, and applies it to the treatment of malignant tumors

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Dissolve 30.0 mg of all-trans retinoic acid, 26.4 mg of vorinostat, 46.2 mg of perifosine, 1.00 g of poloxamer 188, and 7 μl of ethylenediamine in 20 ml of hot ethanol. Under high-speed stirring, the ethanol solution was slowly added to 80 ml of water, and the ethanol was removed by rotary evaporation to obtain nanoparticles dispersed in water.

Embodiment 2

[0025] 300 mg of 9-cis retinoic acid, 26.4 mg of vorinostat, 46.2 mg of perifosine, 400 mg of polycaprolactone, 1.60 g of Tween 80 were dissolved in a mixture consisting of 10 ml of ethanol and 10 ml of acetone. Under high-speed stirring, the above solution was slowly added to 80 ml of water, and the acetone and ethanol were removed by dialysis to obtain nanoparticles dispersed in water.

Embodiment 3

[0027] Dissolve 30 mg of all-trans retinoic acid, 105.6 mg of vorinostat, 46.2 mg of perifosine, and 300 mg of polycaprolactone-polyethylene glycol block copolymer in a mixture consisting of 10 ml of ethanol and 10 ml of acetone. Under high-speed stirring, the above solution was slowly added to 80ml of water, and most of the acetone and ethanol were removed by low-temperature evaporation under vacuum, and then freeze-dried to obtain nanoparticle powder.

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Abstract

The invention relates to a multi-drug delivery retinoic acid nanoparticle solution and application thereof as a tumor treating medicine. Retinoic acid, a histone deacetylase inhibitor, pirenfox, an emulsifier, a substrate and a cosolvent are used as raw materials, and multi-drug delivery retinoic acid nanoparticles are synthesized by a solvent dilution method through one step. In the formula, as auxiliary materials, the substrate, the emulsifier and the cosolvent play roles in stabilizing the nanoparticles and regulating the particle size; as auxiliary drugs, the histone deacetylase inhibitor and the pirenfox are used for reversing the tolerance of tumor cells to retinoic acid medicines; as a main drug, the retinoic acid induces differentiation and apoptosis of the tumor cell. The components complement one another to play a synergistic role. The multi-drug delivery retinoic acid nanoparticle solution is reasonable in drug collocation, clear in acting mechanism and simple in preparation process, has a passive tumor targeting property, and is expected to be applied to the field of tumor treatment.

Description

technical field [0001] The invention relates to a multi-drug co-delivery nanoparticle of retinoic acid and its application as a tumor treatment drug. Background technique [0002] In 1988, Chinese scholars successfully used all-trans retinoic acid (ATRA) for differentiation therapy of acute promyelocytic leukemia, increasing the remission rate of acute promyelocytic leukemia from about 46% of traditional chemotherapy to about 95%. It can be seen that differentiation therapy may be a breakthrough in the radical cure of malignant tumors. However, at present, retinoic acid is only used in the treatment of acute promyelocytic leukemia clinically, but not in the differentiation therapy of other malignant tumors. Although at the cellular level, retinoic acid and its derivatives can indeed induce the differentiation and apoptosis of some solid tumor cells, the effect of retinoic acid on the differentiation of these tumor cells is very limited, and many tumor cells, including acute...

Claims

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Application Information

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IPC IPC(8): A61K9/08A61K9/19A61K47/34A61K31/675A61P35/00A61K31/203A61K31/167A61K31/4406
CPCA61K9/08A61K9/19A61K31/167A61K31/203A61K31/4406A61K31/675A61K47/10A61K47/26A61K47/34A61K2300/00
Inventor 廖瀚孙广炜吕国军张英刘洋赵姗
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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