Preparation and application of cotransport system of Mn<2+> donor and chloroquine drugs

Abstract

The invention relates to preparation and application of a cotransport system of a Mn<2+> donor and chloroquine drugs. According to the preparation and the application, the problems of low pesticide effect, large required dosage, poor targeting ability and serious toxic and side effects of tumor treating drugs can be effectively solved. According to the technical scheme, double-layer hollow mesoporous manganese sesquioxide nanoparticles are synthesized by virtue of a hydrothermal method, hyaluronic acid and the double-layer hollow mesoporous manganese sesquioxide nanoparticles are linked through chemical bonds so as to spontaneously form a nano-layer in a water medium, and then a chloroquine anti-tumor drug enters mesoporous structures of the double-layer hollow mesoporous manganese sesquioxide nanoparticles through a physical effect. According to the drug-cooperated cotransport system, the dosage and toxic and side effects of the drug can be effectively reduced, the treating efficiency of the drug can be improved, the solubility problem of the drug can be effectively solved, and the effective loading of the drug and the controlled release of the drug at target sites of tumors can be realized; the dispersity and biocompatibility of magnetic carriers are improved, the long circle, the active targeting and the fixed-point gate-controlled release of the drug are realized; and furthermore, the preparation process is simple, energy saving, environmentally friendly and low in cost, the industrial production can be realized, and the preparation process is the innovation of the tumor treating drugs.

Description

technical field

[0001] The invention belongs to the field of medicine and chemical industry, especially a kind of Mn 2+ Preparation and application of donor and chloroquine drug co-transport system (i.e. a hollow mesoporous gated Mn 2+ Preparation method and application of donor and chloroquine antineoplastic drug synergistic co-transporter system). Background technique

[0002] 1. Hollow mesoporous gated Mn 2+ Synergistic co-transport of donor and chloroquine antineoplastics significantly enhances therapeutic effect

[0003] Chloroquine (CQ) is an old class of anti-malarial drugs. In recent years, studies have found that the use of chloroquine to inhibit autophagy induced by treatment can promote tumor cell death, lead to tumor degenerative changes, and delay tumor growth. In 1992, Djordevic et al. reported that chloroquine could affect human MDA-MB231 cancer cells through radiosensitization, destabilizing lysosomes and cell membranes. Therefore, chloroquine also has a ...

Examples

Embodiment 1

[0020] Hollow mesoporous gated Mn of the present invention 2+ The preparation method of donor and chloroquine antineoplastic drug synergistic co-transporter system comprises the following steps:

[0021] (1) Synthesis of double-layer hollow mesoporous manganese trioxide nanoparticles: add 16g sucrose to 80mL deionized water, react in an oven at 190°C for 4h, centrifuge at 12000rpm for 10min, and separate the precipitates with deionized water and absolute ethanol. Wash 3 times and dry at 60°C to obtain black carbon powder; weigh 1g of carbon powder, ultrasonically disperse it in 10mL deionized water, add dropwise 40ml of manganese trioxide solution with a mass concentration of 50%, ultrasonically disperse for 15min, and impregnate 48h, stirring, 12000rpm centrifugation for 20min, the precipitate was washed 3 times with deionized water and absolute ethanol, dried at 60°C, and roasted at 450°C for 6h to obtain double-layer hollow mesoporous manganese trioxide nanoparticles; The ...

Embodiment 2

[0025] Hollow mesoporous gated Mn of the present invention 2+The preparation method of donor and chloroquine antineoplastic drug synergistic co-transporter system comprises the following steps:

[0026] (1) Synthesis of double-layer hollow mesoporous manganese trioxide nanoparticles: Add 5 g of sucrose to 10 mL of deionized water, react in an oven at 140°C for 2 h, centrifuge at 12,000 rpm for 8 min, and separate the precipitates with deionized water and absolute ethanol. Wash twice and dry at 60°C to obtain black carbon powder; weigh 0.1g of carbon powder, ultrasonically disperse it in 5mL deionized water, add dropwise 10ml of manganese trioxide solution with a mass concentration of 50%, and ultrasonically disperse for 12min. Immerse for 24 hours, stir, centrifuge at 12,000 rpm for 25 minutes, wash the precipitate twice with deionized water and absolute ethanol, dry at 50°C, and roast at 300°C for 2 hours to obtain double-layer hollow mesoporous manganese trioxide nanoparticl...

Embodiment 3

[0030] Hollow mesoporous gated Mn of the present invention 2+ The preparation method of donor and chloroquine antineoplastic drug synergistic co-transporter system comprises the following steps:

[0031] (1) Synthesis of double-layer hollow mesoporous manganese trioxide nanoparticles: Add 50g sucrose to 200mL deionized water, react in an oven at 300°C for 8h, centrifuge at 12000rpm for 12min, and separate the precipitates with deionized water and absolute ethanol. Wash 3 times and dry at 60°C to obtain black carbon powder; weigh 5g of carbon powder, ultrasonically disperse it in 50mL of deionized water, add dropwise 50ml of manganese trioxide solution with a mass concentration of 50%, ultrasonically disperse for 17min, and impregnate 72h, stirring, 12000rpm centrifugation for 35min, the precipitate was washed 3 times with deionized water and absolute ethanol, dried at 70°C, and roasted at 700°C for 10h to obtain double-layer hollow mesoporous manganese trioxide nanoparticles; ...

technical field

[0001] The invention belongs to the field of medicine and chemical industry, especially a kind of Mn 2+ Preparation and application of donor and chloroquine drug co-transport system (i.e. a hollow mesoporous gated Mn 2+ Preparation method and application of donor and chloroquine antineoplastic drug synergistic co-transporter system). Background technique

[0002] 1. Hollow mesoporous gated Mn 2+ Synergistic co-transport of donor and chloroquine antineoplastics significantly enhances therapeutic effect

[0003] Chloroquine (CQ) is an old class of anti-malarial drugs. In recent years, studies have found that the use of chloroquine to inhibit autophagy induced by treatment can promote tumor cell death, lead to tumor degenerative changes, and delay tumor growth. In 1992, Djordevic et al. reported that chloroquine could affect human MDA-MB231 cancer cells through radiosensitization, destabilizing lysosomes and cell membranes. Therefore, chloroquine also has a ...

Examples

Embodiment 1

[0020] Hollow mesoporous gated Mn of the present invention 2+ The preparation method of donor and chloroquine antineoplastic drug synergistic co-transporter system comprises the following steps:

[0021] (1) Synthesis of double-layer hollow mesoporous manganese trioxide nanoparticles: add 16g sucrose to 80mL deionized water, react in an oven at 190°C for 4h, centrifuge at 12000rpm for 10min, and separate the precipitates with deionized water and absolute ethanol. Wash 3 times and dry at 60°C to obtain black carbon powder; weigh 1g of carbon powder, ultrasonically disperse it in 10mL deionized water, add dropwise 40ml of manganese trioxide solution with a mass concentration of 50%, ultrasonically disperse for 15min, and impregnate 48h, stirring, 12000rpm centrifugation for 20min, the precipitate was washed 3 times with deionized water and absolute ethanol, dried at 60°C, and roasted at 450°C for 6h to obtain double-layer hollow mesoporous manganese trioxide nanoparticles; The ...

Embodiment 2

[0025] Hollow mesoporous gated Mn of the present invention 2+The preparation method of donor and chloroquine antineoplastic drug synergistic co-transporter system comprises the following steps:

[0026] (1) Synthesis of double-layer hollow mesoporous manganese trioxide nanoparticles: Add 5 g of sucrose to 10 mL of deionized water, react in an oven at 140°C for 2 h, centrifuge at 12,000 rpm for 8 min, and separate the precipitates with deionized water and absolute ethanol. Wash twice and dry at 60°C to obtain black carbon powder; weigh 0.1g of carbon powder, ultrasonically disperse it in 5mL deionized water, add dropwise 10ml of manganese trioxide solution with a mass concentration of 50%, and ultrasonically disperse for 12min. Immerse for 24 hours, stir, centrifuge at 12,000 rpm for 25 minutes, wash the precipitate twice with deionized water and absolute ethanol, dry at 50°C, and roast at 300°C for 2 hours to obtain double-layer hollow mesoporous manganese trioxide nanoparticl...

Embodiment 3

[0030] Hollow mesoporous gated Mn of the present invention 2+ The preparation method of donor and chloroquine antineoplastic drug synergistic co-transporter system comprises the following steps:

[0031] (1) Synthesis of double-layer hollow mesoporous manganese trioxide nanoparticles: Add 50g sucrose to 200mL deionized water, react in an oven at 300°C for 8h, centrifuge at 12000rpm for 12min, and separate the precipitates with deionized water and absolute ethanol. Wash 3 times and dry at 60°C to obtain black carbon powder; weigh 5g of carbon powder, ultrasonically disperse it in 50mL of deionized water, add dropwise 50ml of manganese trioxide solution with a mass concentration of 50%, ultrasonically disperse for 17min, and impregnate 72h, stirring, 12000rpm centrifugation for 35min, the precipitate was washed 3 times with deionized water and absolute ethanol, dried at 70°C, and roasted at 700°C for 10h to obtain double-layer hollow mesoporous manganese trioxide nanoparticles; ...