Method for improving target effect of receptor targeting preparation based on folic acid compounds

Abstract

The invention relates to the field of medicinal preparations and particularly relates to a method for improving an active targeting effect of an active targeting preparation based on folic acid compounds by increasing distribution of targeting groups, namely folic acid compound groups, of the active targeting preparation in external water phase. The method is characterized in that the key difference between the method and the conventional preparation method is that normal water, osmotic-pressure regulator solution or neutral buffer saline solution does not serve as the water phase, but alkalescence solution with pH being 7.5-10.0 serves as the water phase. The active targeting effect of the receptor targeting preparation prepared by the method can be improved.

Description

technical field

[0001] The invention relates to the field of pharmaceutical preparations, in particular to a method for increasing the distribution of targeting groups in active targeting preparations based on folic acid compounds, that is, folic acid compound groups, in the external water phase, thereby improving the active targeting effect of the preparations. Background technique

[0002] Folic acid (FA) can be reduced to tetrahydrofolate, which is a coenzyme of one-carbon unit transferase, involved in one-carbon unit metabolism and de novo synthesis of purine and thymine. The expression of folate receptors in normal tissues is highly conserved, only in lung, kidney, choroid and placenta, there is low to moderate expression, and the β subtype is the main one, but in most malignant tumors, such as ovarian cancer, uterus Highly expressed in endometrial cancer, prostate cancer, kidney cancer, breast cancer, lung cancer, colon cancer and nasopharyngeal cancer, sometimes 100-3...

Examples

Embodiment 1

[0036] Weigh 8g of soybean lecithin, 1g of glyceryl trilaurate, 0.2g of DSPE-PEG-FA, and 300mg of doxorubicin, add 200mL of methanol / dichloromethane (1:1, v / v) mixed solvent to dissolve, and rotary evaporate to form a film , adding 300mL of sodium bicarbonate aqueous solution with a pH value of 8.0, hydration at 37°C for 30min, ultrasonic probe, and passing through a 0.22μm microporous membrane to obtain an improved active targeting agent with a particle size of 80.6nm.

Embodiment 2

[0038] Weigh 8 g of soybean lecithin, 1 g of glyceryl trilaurate, 0.2 g of DSPE-PEG-FA, and 200 mg of mitoxantrone, add 200 mL of methanol / dichloromethane (1:1, v / v) mixed solvent to dissolve, and evaporate to obtain Add 300mL of sodium carbonate aqueous solution with a pH value of 8.2 to the membrane, hydrate at 37°C for 30min, sonicate the probe, and pass through a 0.22μm microporous membrane to obtain an improved active targeting agent with a particle size of 85.3nm.

Embodiment 3

[0040] Weigh 8g of soybean lecithin, 1g of glyceryl trilaurate, 0.2g of Chol-PEG-FA, and 100mg of camptothecin, add 200mL of methanol / dichloromethane (1:1, v / v) mixed solvent to dissolve, and rotary evaporate to form a film , adding 300mL of sodium carbonate aqueous solution with a pH value of 8.6, hydrating at 37°C for 30min, ultrasonicating with a probe, and passing through a 0.22μm microporous membrane to obtain an improved active targeting agent with a particle size of 75.4nm.

technical field

[0001] The invention relates to the field of pharmaceutical preparations, in particular to a method for increasing the distribution of targeting groups in active targeting preparations based on folic acid compounds, that is, folic acid compound groups, in the external water phase, thereby improving the active targeting effect of the preparations. Background technique

[0002] Folic acid (FA) can be reduced to tetrahydrofolate, which is a coenzyme of one-carbon unit transferase, involved in one-carbon unit metabolism and de novo synthesis of purine and thymine. The expression of folate receptors in normal tissues is highly conserved, only in lung, kidney, choroid and placenta, there is low to moderate expression, and the β subtype is the main one, but in most malignant tumors, such as ovarian cancer, uterus Highly expressed in endometrial cancer, prostate cancer, kidney cancer, breast cancer, lung cancer, colon cancer and nasopharyngeal cancer, sometimes 100-3...

Examples

Embodiment 1

[0036] Weigh 8g of soybean lecithin, 1g of glyceryl trilaurate, 0.2g of DSPE-PEG-FA, and 300mg of doxorubicin, add 200mL of methanol / dichloromethane (1:1, v / v) mixed solvent to dissolve, and rotary evaporate to form a film , adding 300mL of sodium bicarbonate aqueous solution with a pH value of 8.0, hydration at 37°C for 30min, ultrasonic probe, and passing through a 0.22μm microporous membrane to obtain an improved active targeting agent with a particle size of 80.6nm.

Embodiment 2

[0038] Weigh 8 g of soybean lecithin, 1 g of glyceryl trilaurate, 0.2 g of DSPE-PEG-FA, and 200 mg of mitoxantrone, add 200 mL of methanol / dichloromethane (1:1, v / v) mixed solvent to dissolve, and evaporate to obtain Add 300mL of sodium carbonate aqueous solution with a pH value of 8.2 to the membrane, hydrate at 37°C for 30min, sonicate the probe, and pass through a 0.22μm microporous membrane to obtain an improved active targeting agent with a particle size of 85.3nm.

Embodiment 3

[0040] Weigh 8g of soybean lecithin, 1g of glyceryl trilaurate, 0.2g of Chol-PEG-FA, and 100mg of camptothecin, add 200mL of methanol / dichloromethane (1:1, v / v) mixed solvent to dissolve, and rotary evaporate to form a film , adding 300mL of sodium carbonate aqueous solution with a pH value of 8.6, hydrating at 37°C for 30min, ultrasonicating with a probe, and passing through a 0.22μm microporous membrane to obtain an improved active targeting agent with a particle size of 75.4nm.

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