Preparation method of drug-loading and oxygen-loading hybrid protein nanoparticle, drug-loading and oxygen-loading hybrid protein nanoparticle and application

A technology of hybrid protein and nanoparticle, which is applied in the direction of medical formula, peptide/protein components, medical preparations of non-active ingredients, etc., can solve problems such as central nervous system oxygen poisoning, achieve long storage time, enhance therapeutic effect, and structure stable effect

Active Publication Date: 2018-04-24
SHENZHEN INST OF ADVANCED TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Hyperbaric oxygen therapy supplies oxygen through red blood cells in the blood, but red blood cells cannot penetrate blood vessels to deliver oxygen to the interior of the tumor, and the irregular

Method used

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  • Preparation method of drug-loading and oxygen-loading hybrid protein nanoparticle, drug-loading and oxygen-loading hybrid protein nanoparticle and application
  • Preparation method of drug-loading and oxygen-loading hybrid protein nanoparticle, drug-loading and oxygen-loading hybrid protein nanoparticle and application
  • Preparation method of drug-loading and oxygen-loading hybrid protein nanoparticle, drug-loading and oxygen-loading hybrid protein nanoparticle and application

Examples

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preparation example Construction

[0034] According to the first aspect of the present invention, the present invention provides a method for preparing drug-loaded and oxygen-loaded hybrid protein nanoparticles, comprising the following steps:

[0035] (a) mixing the reducing agent and serum albumin homogeneously, and performing a reduction reaction to obtain reduced serum albumin;

[0036] (b) Mix the reduced serum albumin, hemoglobin and drug homogeneously under aerobic conditions to prepare drug-loaded oxygen-loaded hybrid protein nanoparticles.

[0037] The preparation method of the drug-loaded oxygen-loaded hybrid protein nanoparticles provided by the invention is simple and easy to implement, easy to popularize and apply, and suitable for large-scale preparation.

[0038] In step (a), the reduction reaction between the reducing agent and the serum albumin breaks the disulfide bond inside the serum albumin molecule to obtain the reduced serum albumin molecule in a random state. In step (b), the reduced se...

Embodiment 1

[0076] This example provides a drug-loaded oxygen-loaded hybrid protein nanoparticle, which is prepared according to the following steps:

[0077] (a) Co-dissolve 300mg bovine serum albumin and 30mg dithiothreitol in 5mL deionized water, shake at room temperature for 1 hour, pour the solution into a dialysis bag (3kD), and dialyze in anaerobic deionized water for 12 hours to obtain Reduced serum albumin solution, dilute the reduced serum albumin solution to 6 mL with deionized water to obtain a reduced serum albumin solution with a concentration of 50 mg / mL;

[0078] (b) 20mg of reduced serum albumin solution, 10mg of hemoglobin and 0.8mg of doxorubicin hydrochloride were dissolved in 2mL of pure water under aerobic conditions and homogenized for 10 minutes, adjusted to pH 7 with sodium bicarbonate, and stirred vigorously 2 mL of absolute ethanol was added dropwise to the mixed solution at a speed of 1 mL / min, and after stirring for 0.5 hours, the mixed solution was put into a...

Embodiment 2

[0080] This example provides a drug-loaded oxygen-loaded hybrid protein nanoparticle, which is prepared according to the following steps:

[0081] (a) 300mg human serum albumin and 300mg homocysteine ​​were co-dissolved in 5mL deionized water, shaken at room temperature for 1 hour, poured the solution into a dialysis bag (3kD), and dialyzed in anaerobic deionized water for 12 hours to obtain Reduced serum albumin solution, dilute the reduced serum albumin solution to 6 mL with deionized water to obtain a reduced serum albumin solution with a concentration of 50 mg / mL;

[0082] (b) 20 mg of reduced serum albumin solution, 0.4 mg of hemoglobin and 0.8 mg of doxorubicin hydrochloride were co-dissolved in 2 mL of pure water under aerobic conditions and homogenized for 180 minutes, and the pH value was adjusted to 9 with sodium bicarbonate. Under stirring, 5 mL of absolute ethanol was added dropwise to the mixed solution at a speed of 1 mL / min. After stirring for 12 hours, the solu...

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Abstract

The invention provides a preparation method of a drug-loading and oxygen-loading hybrid protein nanoparticle, the drug-loading and oxygen-loading hybrid protein nanoparticle and application and relates to the technical field of biological pharmacy. The preparation method comprises the following steps: firstly, mixing a reducing agent with serum albumin, homogenizing and carrying out reduction reaction to obtain reduced serum albumin; secondly, mixing the reduced serum albumin, hemoglobin and a drug under the aerobic condition, and homogenizing to prepare the drug-loading and oxygen-loading hybrid protein nanoparticle. According to the drug-loading and oxygen-loading hybrid protein nanoparticle, the technical problems that oxygen cannot be conveyed into tumors by adopting an existing inhalation high-pressure oxygen mode for supplying oxygen, and lung and a central nervous system suffer from oxygen poisoning caused by high-concentration oxygen are alleviated; the oxygen and a drug are conveyed into the tumors by the drug-loading and oxygen-loading hybrid protein nanoparticle in a targeted manner, and drug enrichment is improved; besides, reversible release of oxygen molecules can berealized according to oxygen concentration of a micro-environment; in addition, no side effects are generated; the technical effects that integration of tumor oxygen increase and drug transfer is realized, and the bioavailability of the drug is improved are achieved.

Description

technical field [0001] The invention relates to the technical field of biopharmaceuticals, in particular to a preparation method of drug-loaded oxygen-loaded hybrid protein nanoparticles, drug-loaded oxygen-loaded hybrid protein nanoparticles and applications. Background technique [0002] Solid tumors exhibit hypoxic microenvironment characteristics due to chaotic and complex vascular structures and vigorous cell metabolism. Studies have shown that tumor hypoxia creates a special tumor microenvironment, which affects tumor angiogenesis, cell division and other processes. , resulting in insensitivity to chemotherapy drugs and radiotherapy, and even lead to tumor gene mutation and tumor metastasis. In photodynamic therapy, oxygen as a reactant has a certain influence on the effect of tumor photodynamic therapy. Tumor hypoxia limits the production of active oxygen in photodynamic therapy, which affects the therapeutic effect. [0003] At present, the clinical treatment adopts...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K38/42A61K47/64A61K9/14A61K47/42A61P35/00A61K31/704A61K31/519A61K31/122
CPCA61K9/146A61K31/122A61K31/519A61K31/704A61K38/42A61K41/0057A61K41/0071A61K2300/00
Inventor 蔡林涛罗震宇郑明彬陈志宽田浩陈泽
Owner SHENZHEN INST OF ADVANCED TECH
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