Irinotecan liposome and preparation method thereof
A technology of liposome preparation and Kangzhi, which is applied in the field of medicine
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Embodiment 1
[0008] Example 1 Preparation of blank liposomes
[0009] In order to avoid the influence of the organic solvent in the preparation process, dichloromethane was used to dissolve the lipid, and the blank liposome was prepared by the film dispersion method.
[0010] Blank liposome prescription
[0011] Hydrogenated soybean lecithin (HSPC) 3g
[0012] Cholesterol (CH) 1g
[0013] mPEG 2000 -DSPE 0.75g
[0014] Combine HSPC, CH, mPEG 2000 -DSPE is dissolved in dichloromethane, and the dichloromethane is removed according to the film method to obtain a lipid film. Add ammonium ethylenediaminetetraacetate (NH 4 EDTA) solution, and stirred in a water bath at 65°C for 20 min to obtain the primary blank liposome. Sonicate the primary product probe for 8 min (200 w×2 min, 400 w×6 min), and then pass through 0.8 μm, 0.45 μm, 0.22 μm microporous membranes in turn to obtain a blank liposome suspension.
Embodiment 2
[0015] Example 2 Blank liposome gradient establishment and drug loading
[0016] The methods for gradient establishment include "ion exchange resin method", "dialysis method" and "molecular sieve separation method". The ion-exchange resin method is used as an example to illustrate below.
[0017] Take 0.3 mL of the blank liposome suspension of "Example 1", and load it on a 3 mL anion-cation mixed ion exchange resin column pretreated by centrifugation (wet packing, the volume ratio of anion resin to cation resin is 2: 1 ), centrifuged at 2000 rpm for 4 min to obtain 4 Blank liposome suspension with EDTA transmembrane ion gradient.
[0018] Drug loading: Take 0.1 mL of the above gradient liposomes, add 0.3 mL of CPT-11 solution (3.0 mg / mL), and incubate at 60 °C for 10 min to prepare CPT-11 liposomes.
Embodiment 3
[0019] Example 3 The impact of ethanol on the particle size of blank liposomes
[0020] Measure a certain volume of "Example 1" blank liposome, add 0.0%, 0.1%, 1%, 5.0%, 10.0%, 15%, 20.0%, 25.0% (v / v) ethanol respectively, and mix well After that, the particle size was measured at 0, 4, 8, and 24 h, and the results are shown in Table 1. Adding 5.0% and 10.0% ethanol had no significant effect on liposome particle size within 24 h; however, the particle size increased after adding 20.0% and 25.0% ethanol for 24 h.
[0021] Table 1 Effect of ethanol on the particle size of blank liposomes
[0022] Ethanol concentration (v / v) 0% 0.1% 1% 5% 10% 15% 20% 25% Particle size (0 hour) 85.9 87.3 90.5 88.1 83.7 92.6 99.5 104.0 Particle size (24 hours) 86.1 86.2 89.6 89.6 87.6 97.1 105.2 109.3
[0023] It can be seen from the table that when the ethanol is greater than 15%, the particle size increases.
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