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Albumin nano-particles and preparation method and use thereof

An albumin nanoparticle and albumin technology, which is applied in pharmaceutical formulations, medical preparations containing active ingredients, organic active ingredients, etc., can solve the problems of poor water solubility of paclitaxel, allergic reactions in patients with castor oil, etc. The effect of enhancing drug-carrying capacity and promoting cell apoptosis

Active Publication Date: 2017-09-15
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to paclitaxel's poor water solubility a surfactant such as castor oil must be used
But castor oil often causes severe allergic reactions in patients

Method used

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  • Albumin nano-particles and preparation method and use thereof
  • Albumin nano-particles and preparation method and use thereof
  • Albumin nano-particles and preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0059] Preparation Example 1: Synthesis of Low Molecular Weight Protamine Modified Albumin

[0060] 1. Activation of Albumin

[0061] Weigh 5 mg SMCC and dissolve it in 200 μl of anhydrous DMSO, weigh 200 mg bovine serum albumin (BSA) and dissolve it in the phosphate buffered saline solution of pH 7.2, after the dissolution is complete, add the SMCC solution dropwise to the BSA solution, After stirring at room temperature for 1 h, the product was purified by FPLC molecular sieves with a detection wavelength of 280 nm and a flow rate of 1 ml / min. First connect Desalting and FPLC, use 0.1M phosphate buffer (pH7.2) as the mobile phase to equilibrate the column for about 4-5 column volumes, that is, 40-50ml, then inject the reaction product into the injection loop, and After the ultraviolet baseline is adjusted to zero, the sample enters the Desalting at a speed of 1ml / min, and after about 3 minutes, the eluted ultraviolet peak is collected by the instrument through the program s...

preparation Embodiment 2

[0066] Preparation Example 2: Preparation of Albumin Nanoparticles and Albumin Nanoparticles Modified by Low Molecular Weight Protamine

[0067] Prepare the urea solution:

[0068] Dissolve 3.0g Tris base and 28.0g urea in water, adjust the pH to 8.3 with concentrated hydrochloric acid, and set aside. Weigh 100mg of BSA and the above-prepared BSA-LMWP, dissolve them in 400μl of water, transfer them to 5.6ml of urea solution and mix them evenly, then add 1.05ml of absolute ethanol and mix them evenly, add sodium borohydride solution, and finally The concentration range is 0.01-0.1mol / L, and then centrifuged at 8000rpm for 3min, followed by 30min at room temperature, 30min in a 50°C water bath, and placed at room temperature for later use to prepare BSA-denatured urea solution and BSA-LMWP-denatured urea solution.

[0069] Preparation of blank nanoparticles:

[0070] Take 0.1ml of absolute ethanol and add it dropwise to the above BSA-denatured urea solution or BSA-LMWP denatur...

experiment Embodiment 1

[0073] Experimental Example 1: In vitro characterization experiments of albumin nanoparticles and albumin nanoparticles modified with low molecular weight protamine

[0074] (1) Particle size and potential

[0075] Take 100 μl each of purified albumin nanoparticles (BSA NP) and low molecular weight protamine-modified albumin nanoparticles (L-BSA NP), dilute with purified water to a final volume of 1ml, and use a Malvern particle size analyzer Determination of particle size and potential, the results are as follows image 3 with Figure 5 shown.

[0076] (2)TEM

[0077] Add albumin nanoparticles (BSA NP) and low-molecular-weight protamine-modified albumin nanoparticles (L-BSA NP) onto the pre-hydrated copper grid respectively, blot dry after 1 min, and add acetate glaze for negative staining Let it dry naturally after 1 min. Determination and analysis of albumin nanoparticles by transmission electron microscope, the results are as follows: Figure 4 shown.

[0078] (3) I...

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Abstract

The invention relates to a preparation method for albumin nano-particles and the albumin nano-particles prepared by the method and a pharmaceutical use of the albumin nano-particles. The preparation method comprises the following steps: 1) dissolving the albumin in urea solution, uniformly mixing, adding sodium borohydride solution to obtain the urea solution of albuminate; and 2) adding absolute ethyl alcohol or other organic solvents to the urea solution of the albuminate, and adding purified water, namely forming the albumin nano-particles. In addition, the invention further relates to the albumin nano-particles prepared by the method and the pharmaceutical use of the albumin nano-particles.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically, the invention relates to an albumin nanoparticle and its preparation method and application. Background technique [0002] Glioma is the most important tumor in central nervous system diseases, accounting for about 40%, mainly divided into glioblastoma and anaplastic astrocytoma. In the past few years, although the level of traditional treatment methods (such as surgery, radiotherapy and chemotherapy) has improved a lot, the survival time of brain tumor patients has not been significantly improved, and it is still less than two years. Chemotherapy is still the main way to treat glioma. However, due to the existence of the blood-brain barrier in chemotherapy, the local drug concentration in the tumor is low, and the toxic and side effects of chemotherapy drugs are obvious, so the curative effect is not good. In general, the combination of two or more drugs is a promising strateg...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K45/00A61K47/42A61K31/167A61K31/337A61P35/00
CPCA61K9/5169A61K31/167A61K31/337A61K45/00
Inventor 黄永焯蔺婷婷姜一帆
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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