Preparation method of lipid wrapped solid drug nano particle
A nanoparticle and drug technology, applied in the field of biomedicine, can solve the problem of low drug loading of nano drugs, achieve the effect of small batch-to-batch differences and great application prospects
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[0032] Example 1 Preparation of methotrexate nanoparticle solution
[0033] Weigh methotrexate, dissolve it in a mixed solvent of N,N-dimethylformamide and N-methylpyrrolidone (volume ratio 7:3), and prepare a 4 mg / mL organic solution of methotrexate. It is introduced into the first channel of the four-channel vortex mixer, and ultrapure water is introduced into the other three channels to achieve rapid turbulent mixing to prepare the methotrexate nanoparticle solution. The volume ratio of the organic methotrexate solution and the aqueous phase is 1:3 to 9, respectively, and the flow rate of the organic phase is 6 mL / min.
[0034] When the volume ratio of the organic methotrexate solution (organic phase) and the aqueous phase is changed, methotrexate nanoparticles with different particle sizes can be prepared. The specific ratio and particle size relationship are as follows: figure 1 As shown in the figure, it can be seen from the figure that when the volume ratio of the orga...
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[0037] Example 2 Preparation of lipid-encapsulated methotrexate nanoparticles
[0038]Weigh 1,2-dioleoyl-SN-glycerol-3-phosphorylethanolamine (DOPE), cholesterol succinate monoester (CHEMS), 1,2-distearyl-SN-glycerol-3-phosphorylethanolamine -Polyethylene glycol (2000) (DSPE-PEG), made into a mixture in a molar ratio of 10:9:1, dissolved in dichloromethane to make a 10 mg / mL mixed lipid solution for later use. Quantitatively pipette 0.1 mL of mixed lipid dichloromethane solution into 10 mL of 4% ethanol solution, and the solution is sonicated with a probe sonicator until it is clear for use. After mixing the lipid ethanol solution of equal volume and the methotrexate nanoparticle solution with a particle size of 49.1 nm prepared in Example 1, the mass ratio of methotrexate and the mixed lipid in the mixed solution was 4:1, and the mixed solution was mixed. The liquid was repeatedly extruded 7 times through a 100-nm polyvinylidene fluoride membrane to obtain lipid-encapsulated...
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[0045] Example 3 Preparation of lipid-encapsulated chlorambucil or doxorubicin nanoparticles
[0046] Weigh chlorambucil or doxorubicin and dissolve them in dimethyl sulfoxide or N,N-dimethylformamide, respectively, to prepare an organic solution of 1 mg / mL or 0.5 mg / mL, respectively, and introduce them into The first channel of the four-channel vortex mixer, and the other three channels introduce ultrapure water to achieve fast turbulent mixing to prepare chlorambucil nanoparticle solution and doxorubicin nanoparticle solution. Among them, the volume ratio of the chlorambucil nanoparticle solution (organic phase) or the doxorubicin nanoparticle solution (organic phase) and the aqueous phase was set to 1:3 to 11, respectively, and the flow rate of the organic phase was 10 mL / min. A chlorambucil nanoparticle solution and a doxorubicin nanoparticle solution were obtained.
[0047] Referring to the steps in Example 2, lipid-coated chlorambucil nanoparticles and lipid-coated doxo...
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