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Protein micro/nano sphere carrying antitumor chemotherapeutic medicine and preparation method of protein micro/nano sphere

A chemotherapeutic drug and micro-nanosphere technology, which is applied in the field of protein micro-nanospheres and the preparation method thereof, can solve the problems of short half-life of TNFSF protein, influence the pharmacokinetic characteristics of drugs and the like, and achieve the effect of high encapsulation rate

Active Publication Date: 2013-08-21
BEIJING BIOHELIX BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report of making suitable micro-nanospheres of TNFSF protein and insoluble antitumor drugs in the prior art
[0009] In addition, the TNFSF protein represented by TRAIL also has the defect that the half-life is too short, which will affect the pharmacokinetic characteristics of the drug in vivo

Method used

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  • Protein micro/nano sphere carrying antitumor chemotherapeutic medicine and preparation method of protein micro/nano sphere
  • Protein micro/nano sphere carrying antitumor chemotherapeutic medicine and preparation method of protein micro/nano sphere
  • Protein micro/nano sphere carrying antitumor chemotherapeutic medicine and preparation method of protein micro/nano sphere

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] Example 1 TRA-DOC micro-nano balls

[0092] Experimental Materials:

[0093] Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), expressed and extracted by Escherichia coli. Paclitaxel (purity ≥98.00%); ethyl acetate; PBS buffer solution; deionized water.

[0094] laboratory apparatus:

[0095] Ultrasonic crusher, high-speed centrifuge, Zeta potential meter with submicron particle size analysis function, cold field emission scanning electron microscope, flow cytometer, laser confocal microscope, X-ray photoelectron diffraction, high performance liquid chromatography, Circular dichroism spectrometer, SPG membrane emulsifier.

[0096] experiment procedure:

[0097] Dissolve 20mg paclitaxel (DOC) in 20ml ethyl acetate to make a 1mg / mL solution as the oil phase, dissolve 50mg TRAIL in 50ml water to make a 1mg / mL solution as the water phase, and use The oil phase was dispersed in the water phase by ultrasonic crushing to prepare the oil / wa...

Embodiment 2

[0101] Example 2 HSA-DOC micro-nanospheres

[0102] Experimental Materials:

[0103] Human serum albumin (HSA), expressed and extracted by Escherichia coli. Paclitaxel (purity ≥98.00%); ethyl acetate; PBS buffer solution; deionized water.

[0104] laboratory apparatus:

[0105] Ultrasonic crusher, high-speed centrifuge, Zeta potential meter with submicron particle size analysis function, cold field emission scanning electron microscope, SPG membrane emulsifier.

[0106] experiment procedure:

[0107] Dissolve 20mg of paclitaxel (DOC) in 20ml of ethyl acetate to make a 1mg / mL solution as the oil phase, and dissolve 50mg of HSA in 50ml of water to make a 1mg / mL solution as the water phase. The oil phase was dispersed in the water phase by ultrasonic crushing to prepare the oil / water primary emulsion. Pour this primary emulsion into a rapid membrane emulsification device, press it repeatedly through the membrane pores of the SPG membrane (pore size 800-1000nm) at room temper...

Embodiment 3

[0109] Example 3 TNF-α and DOC micro-nanospheres

[0110] Experimental Materials:

[0111] TNF-α, expressed and extracted by Escherichia coli. Paclitaxel (purity ≥98.00%); ethyl acetate; PBS buffer solution; deionized water.

[0112] laboratory apparatus:

[0113] Ultrasonic crusher, high-speed centrifuge, Zeta potential meter with submicron particle size analysis function, cold field emission scanning electron microscope, SPG membrane emulsifier.

[0114] experiment procedure:

[0115] Dissolve 20mg of paclitaxel (DOC) in 20ml of ethyl acetate to make a 1mg / mL solution as the oil phase, and dissolve 50mg of TNF-α in 50ml of water to make a 1mg / mL solution as the water phase. , using ultrasonic crushing to disperse the oil phase in the water phase to prepare the oil / water primary emulsion. Pour the primary emulsion into a rapid membrane emulsification device, and repeatedly press it through the SPG membrane with a pore size of 800nm ​​under a nitrogen pressure of 0.8MPa a...

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Abstract

The invention relates to a protein micro / nano sphere carrying an antitumor chemotherapeutic medicine. The composition preferably comprises a housing and a core on the premise that the protein is TNFSF (Tumor Necrosis Factor Superfamily) protein, and the antitumor chemotherapeutic medicine is an indissolvable medicine; the housing is composed of the TNFSF protein and is basically completely closed; the core is placed into the housing and contains the antitumor chemotherapeutic medicine; and the maximum diameter of the housing is less than 500nm. The protein micro / nano sphere carrying the antitumor chemotherapeutic medicine has the beneficial effects that the protein micro / nano sphere which is prepared based on the membrane emulsification technology and can carry an indissolvable antitumor chemotherapeutic medicine is provided; and the invention particularly provides a preparation method of the protein micro / nano sphered of the TNFSF protein and HAS (Human Serum Albumin) protein, represented by TRAIL (Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand).

Description

technical field [0001] The invention belongs to the field of anti-tumor drugs, in particular to protein micro-nano balls carrying anti-tumor chemotherapeutic drugs and a preparation method thereof. Background technique [0002] Micro-nanospheres refer to the nano-scale dispersion system formed by dispersing or adsorbing drugs in polymer and polymer matrices, with a size of 10-1000nm. According to different carriers, they can be divided into polycyanoacrylate nanoparticles, white Different types of protein nanoparticles, polylactic acid nanoparticles, lipid nanoparticles, etc. [0003] Making proteins or peptides into micro-nanospheres for system administration can not only effectively prevent the drug from degrading quickly in the body, but also target and deliver it to effective parts in the body to achieve the purpose of sustained release and long-term effect. However, problems such as poor protein stability, low encapsulation efficiency, small drug loading capacity, easy...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/42A61K45/00A61K31/337A61P35/00
Inventor 不公告发明人
Owner BEIJING BIOHELIX BIOTECH CO LTD
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