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Targeted administration preparation of epipodophyllotoxins medicine

A podophyllotoxin and drug technology, applied in the field of medicine, can solve the problems of non-targeting liver tissue, and achieve the effect of facilitating treatment, reducing toxicity, and eliminating allergic reactions

Active Publication Date: 2015-04-22
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Moreover, albumin is coated on the surface of drug nanoparticles, and its physiological function has not changed. It can target receptors such as gp60 of tumor cells, but it does not have tissue targeting of liver and lung.

Method used

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  • Targeted administration preparation of epipodophyllotoxins medicine
  • Targeted administration preparation of epipodophyllotoxins medicine
  • Targeted administration preparation of epipodophyllotoxins medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Take 50 mg of human serum albumin, add 10 ml of water for injection and dissolve to obtain a human serum albumin solution. Take 10 mg of teniposide, add 50 mg of egg yolk lecithin E80, dissolve in about 10 ml of methanol, and stir at 40°C for 1 to 2 hours to obtain a light yellow clear solution. Remove methanol by rotary evaporation to obtain teniposide phospholipid complex, dissolve it with 1ml of dichloromethane, mix it with the above-mentioned human serum albumin solution, and ultrasonically probe for 1min to make a suspension, and then place the suspension in high-pressure milk Homogenize in the homogenizer for 5 times, then spin-evaporate it to remove the organic solvent to obtain a nanoparticle solution. The particle size of the albumin nanoparticles is 138.3nm and the PDI is 0.127 as measured by a laser particle size analyzer. The particle size distribution diagram is shown in figure 1 .

Embodiment 2

[0080] Take 200 mg of human serum albumin, add 10 ml of water for injection and dissolve to obtain a human serum albumin solution. Take 10 mg of etoposide, add 50 mg of egg yolk lecithin E80, dissolve in about 10 ml of methanol, and stir at 40°C for 1 to 2 hours to obtain a light yellow clear solution. The etoposide phospholipid complex was obtained by rotary evaporation to remove methanol, and the DSC spectra of teniposide, phospholipids, etoposide phospholipid complex, and physical mixture of etoposide and phospholipids were respectively measured by differential scanning calorimetry, see Figure 2-1 to Figure 2-4 shown. Dissolve the etoposide phospholipid complex with 1ml of chloroform, mix it with the above-mentioned human serum albumin solution, and ultrasonically probe the probe for 1 min to make a suspension, then milk the suspension 10 times in a high-pressure homogenizer, and spin it Evaporation to remove the organic solvent yielded a nanoparticle solution with a part...

Embodiment 3

[0082] Take 400 mg of human serum albumin, add 10 ml of water for injection: ethanol = 9:1 and dissolve in a mixed solvent to obtain a human serum albumin solution. Take 10 mg of etoposide hydrochloride, add 5 mg / ml of NaHCO 3 To 100 μl of the solution, add 200 mg of egg yolk lecithin E80 and dissolve in about 10 ml of methanol, and stir at 40°C for 1 to 2 hours to obtain a light yellow clear solution. Remove the methanol by rotary evaporation to obtain the etoposide phospholipid complex, dissolve it with 1ml of dichloromethane, mix it with the above human serum albumin solution, and ultrasonically probe the probe for 1min to make a suspension, and then put the suspension in high-pressure milk to homogenize Emulsion in the container for 5 times, then rotary steaming to remove the organic solvent to obtain a nanoparticle solution with a particle size of 201.8nm and a PDI of 0.225.

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Abstract

The invention discloses a phospholipid complex albumin nanoparticle containing epipodophyllotoxins medicine. The nanoparticle contains a complex formed by epipodophyllotoxins medicine and phospholipid and albumin. The nanoparticle comprises the following raw materials in parts by weight: 1 part of epipodophyllotoxins medicine, 1-50 parts of phospholipid and 2-100 parts of albumin. The phospholipid complex albumin nanoparticle can be used for remarkably reducing the toxicity of the epipodophyllotoxins medicine, especially bone marrow suppression; meanwhile, the phospholipid complex albumin nanoparticle has liver-lung targeting property.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a targeted drug delivery preparation of podophyllotoxin, in particular to phospholipid complex albumin nanoparticles of podophyllotoxin and derivatives thereof. Background technique [0002] Podophyllotoxin is a lignan isolated from the rhizome of Podophyllum genus Podophyllum in the Berberidaceae family. It has a chemical structure of 2,3-butyrolactone-4-aryltetrahydronaphthalene, and is effective on microtubules and tumors. The cells have an inhibitory effect, but the toxicity is high, so it is not suitable for direct clinical application. The currently commercially available podophyllotoxin drugs mainly include etoposide and teniposide, which are mainly used for malignant lymphoma, Hodgkin's disease, acute lymphocytic leukemia, empty angiothemoma, and glioblastoma , astrocytoma, bladder cancer, neuroblastoma and other solid tumors in children, and is also used to treat small c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K31/7048A61K31/365A61K47/42A61K47/24A61P35/00
Inventor 龚涛张志荣和心依
Owner SICHUAN UNIV
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