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Nanometer granule prepn of cinobufagin toxoprotein and its prepn process

A technology of albumin nanoparticles and cinobufaction base, applied in the field of medicine, can solve the problems of surfactant residues, organic solvent residues, limited reliability, etc., achieve less organic solvent residues, reduce toxic side effects, and narrow particle size distribution Effect

Active Publication Date: 2006-05-17
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some existing methods for preparing albumin nanoparticles often have disadvantages such as difficulty in controlling the particle size, large residual or unstable surfactants, etc. For example, if the heat-denatured emulsification method is used, an organic solvent is required to remove the oily residue and surface Active agents not only easily cause the residue of organic solvents, but also make it difficult to purify nanoparticles, and the particle size is difficult to control, and it is also unfavorable for thermally unstable drugs.
If the pH-aggregation method is used, the particle size of albumin nanoparticles is also difficult to control, and the pH value needs to be adjusted under salt-free conditions. However, in the presence of high concentrations of protein, the reliability of measuring the pH value with a glass electrode is limited.
In view of the above reasons, there have been no reports of cinobufaction-based albumin nanoparticle preparations so far.

Method used

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  • Nanometer granule prepn of cinobufagin toxoprotein and its prepn process
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  • Nanometer granule prepn of cinobufagin toxoprotein and its prepn process

Examples

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Embodiment 1

[0031] Example 1. Preparation of Cinobufin-based Albumin Nanoparticle Preparation

[0032] Dissolve 50mg of albumin in 2ml of water, dissolve 5mg of cinobufaction in 1ml of ethanol, add cinobufaction alcohol solution into the albumin aqueous solution, control the pH value between 5-7, stir at 0.5 Continuously add 3ml of ethanol at the rate of ml / min to form a milky colloidal suspension. Stir 27μl of cross-linking agent glutaraldehyde. Stir continuously for 24 hours to promote the cross-linking and solidification of nanoparticles. Gently heat and evaporate under reduced pressure to remove organic solvents such as ethanol. Freeze-dry to obtain the Cinobufacien-based nanoparticle preparation of the present invention.

Embodiment 2

[0033] Example 2 Preparation of Cinobufin-based Albumin Nanoparticle Preparation

[0034] Dissolve 100mg of albumin in 4ml of 10mM NaCl solution, dissolve 20mg of cinobufacin in 2ml of ethanol, add cinobufin in alcohol solution to the albumin solution, control the pH between 5-7, and stir Continue to add an appropriate amount of dehydrating agent acetone until the formation of a milky colloidal suspension, add an appropriate amount of cross-linking agent methyl polyethylene-dextran under stirring to form a milky white opaque liquid, continue stirring for 26 hours to promote the cross-linking and curing of nanoparticles, and slightly heat Evaporate under reduced pressure, remove organic solvents such as ethanol and acetone, and freeze-dry to obtain the Cinobufagini toxin-based nanoparticle preparation of the present invention.

[0035] Observation of appearance and morphology: using tungsten phosphate negative staining method, observing the appearance and morphology of the cino...

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Abstract

The present invention relates to medicine technology, and is nanometer granular cinobufagin-albumin preparation as one new preparation form of cinobufagin and its preparation process. Cinobufagin has high antitumor effect but high toxicity and short intracorporeal half life. The nanometer granular cinobufagin-albumin preparation of the present invention has round shape of nanometer grains, narrow grain size distribution in the range of 50-250 nm, average grain size of 125.9 nm, liver targeting and delayed releasing, so that it has raised curative effect and lowered toxicity and may be used in preparing medicine for treating liver cancer.

Description

technical field [0001] The invention relates to the technical field of medicine, and relates to a cinobufagin albumin nanoparticle preparation and a preparation method thereof. Background technique [0002] Cinobufagin is a component in animal toads, and its chemical structure is as follows: [0003] [0004] In vitro experiments have confirmed that it has a good anti-tumor effect, and experiments have also confirmed that its killing and inhibiting effect on tumors within a certain concentration range is positively linearly correlated with its action time. (Su Yonghua, Yin Xicai, Xie Juemin, et al. "Inhibitory effects of three bufo toxin monomers on the growth of SMMC-7721 and BEL-7402 human liver cancer cells". Journal of Second Military Medical University. 2003, 24(4). 393-395) However, the Cinobufati toxin base is highly toxic and has a short half-life in the body. After administration, the drug is widely distributed in multiple organs su...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/38A61K9/14A61K35/65A61P35/00
Inventor 凌昌全苏永华
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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