Nanocrystal of camptothecin drugs and preparation method thereof
A camptothecin and nanocrystal technology, which is applied in the field of nanocrystals of camptothecin drugs, can solve the problems of affecting the therapeutic effect of drugs, large nanometer particle size, and increased gastrointestinal toxicity.
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example 1
[0041] Weigh 25mg of hydroxycamptothecin and dissolve it in 2mL of sodium hydroxide solution (0.1mol·L-1), and slowly add dilute hydrochloric acid solution (0.1mol·L-) to the syringe pump controller under ultrasonic conditions (25℃, 250W). 1) Control speed: first 2mL / min×0.5min, then 1.0mL / min×0.5min, then 0.5mL / min×0.6min (pH=5 at this time), centrifugation (centrifugation radius 5cm, 1000rpm centrifugation for 10min); Take the supernatant, continue to drop 0.2 mL of dilute hydrochloric acid solution (0.1 mol·L-1) at a rate of 0.5 mL / min to pH=4, and then centrifuge again (1000 rpm for 10 min). The sediments after two centrifugation were combined, 5mL purified water was added to resuspend, and homogenized under high pressure (25°C, 2×105KPa) 8 times. The obtained nanocrystalline particle size is 133.5±0.3nm ( figure 1 ), the polydispersity index (PDI) is 0.13±0.02.
[0042] Add 25% of the total weight of the lyophilized protective agent P188, freeze-dried and stored at 4°C, rec...
example 2
[0044] Weigh 1000.0 mg of hydroxycamptothecin and dissolve it in 40.0 mL of sodium hydroxide solution (0.2mol·L-1), and slowly add dilute hydrochloric acid solution (0.2mol·L-1) to the syringe pump controller under ultrasonic conditions (25℃, 250W). L-1), control speed: first 2mL / min×10min, then 1.0mL / min×10min, then 0.5mL / min×10min (at this time pH=5), centrifugation (centrifugal radius 5cm, 1000rpm centrifugation for 10min); take Supernatant, continue to drop 5.0 mL of dilute hydrochloric acid solution (0.2 mol·L-1) at a rate of 0.5 mL / min to pH=4, and then centrifuge again (centrifugation radius 5 cm, 1000 rpm centrifugation for 10 min). Combine the sediments after two centrifugation, add 80 mL of purified water to resuspend, and homogenize at high pressure (25°C, 2×105KPa) 8 times. The particle size measured by the particle size / potentiometer is (141.0±0.4)nm ( figure 2 ), the PDI value is 0.14±0.02, and the potential is (-26.0±1.1)mV.
example 3
[0046] Weigh 25mg of 7-ethyl-10 hydroxycamptothecin and dissolve it in 2mL of sodium hydroxide solution (0.1mol·L-1), and slowly drop the dilute hydrochloric acid solution with the syringe pump controller under ultrasonic conditions (25℃, 250W) (0.1mol·L-1), control speed: first 2mL / min×0.5min, then 1.0mL / min×0.5min, then 0.5mL / min×0.6min (at this time pH=5), centrifuge (centrifugation radius 5cm Centrifuge at 1000 rpm for 10 min); take the supernatant, continue to drop 0.2 mL of dilute hydrochloric acid solution (0.1 mol·L-1) at a rate of 0.5 mL / min to pH = 4, and then centrifuge again (at 1000 rpm for 10 min). The sediments after two centrifugation were combined, 5mL purified water was added to resuspend, and homogenized under high pressure (25°C, 2×105KPa) 8 times. The obtained nanocrystalline grain size is 106.7±0.53nm ( image 3 ), the polydispersity index (PDI) is 0.185±0.012, and the potential is (-35.1±1.0) mV.
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