Preparation method of novel albumin nano medicament under mild condition of 37 DEG C

An albumin nanometer and albumin technology, applied in the field of biomedical engineering nanomedicine, can solve problems such as adverse effects of loading, and achieve the effects of good serum stability and storage stability

Inactive Publication Date: 2019-05-21
四川载荧生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In recent years, there have been many albumin nanomedicines in the industry that use the intermolecular sulfhydryl groups of albumin to form a disulfide bond network. However, due to the use of cross-linking agents, temperature, and organic reagents, it is unfavorable for the loading of some heat-sensitive drugs and protein drugs. influences

Method used

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Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0029] A preparation method of novel albumin nanomedicine under mild conditions at 37°C, the operation steps are as follows:

[0030] 1) preparing an albumin aqueous solution with a volume mass concentration of 10-80 mg / mL;

[0031] 2) Configure a reducing agent solution of 1-1000mM (the concentration of the reducing agent solution only needs to be between 1-1000mM), add it to the albumin aqueous solution, and make the reducing agent in the reducing agent solution and the albumin in the albumin aqueous solution The molar ratio is 10:1-100:1 to obtain a reaction system, and a protein denaturant solution with a mass fraction of 0.01%-3% is added to the reaction system to obtain a preliminary mixed solution, which is reacted at 30-80°C for 0.5 After h-6h, the reduced albumin solution exposed to sulfhydryl groups is obtained;

[0032] 3) Dialyzing or ultrafiltering the reduced albumin solution obtained in step 2) at room temperature to remove unreacted reducing agent and protein ...

Embodiment

[0040] A preparation method of novel albumin nanomedicine under mild conditions at 37°C, the operation steps are as follows:

[0041] 1) Prepare an aqueous albumin solution with a mass concentration of 10-80 mg / mL;

[0042] 2) configure the reducing agent solution, the reducing agent solution includes reducing glutathione, cysteine ​​and vitamin C, and make the molar concentration of the reducing agent solution between 50mM-1000mM, add the prepared reducing agent solution to the white In the protein aqueous solution, the molar ratio of the reducing agent in the reducing agent solution to the albumin in the albumin aqueous solution is 50:1-100:1 to obtain a reaction system; a protein denaturant solution with a mass concentration of 1%-3% is prepared , so that it accounts for 0.05%-2% of the concentration of the reaction system, and the protein denaturant solution is added to the reaction system to obtain a preliminary mixed solution, which is reacted at a temperature of 40-70°C...

experiment example 1

[0049] Experimental example 1: Preparation of stable human serum protein nanoparticles cross-linked by disulfide bonds

[0050] Dissolve 40mg of human serum protein powder in 5mL of deionized water, filter or centrifuge to remove flocculent insoluble matter. Add 3mL aqueous solution of reduced glutathione with a molar concentration of 100mM to the human serum protein system, and stir evenly. Add 50 microliters of 8% sodium lauryl sulfate aqueous solution to the human serum albumin system, stir for 2 minutes, and mix well. The reaction solution was poured into a screw-top glass bottle and screwed tightly, placed in a water bath at 50°C for heating, and stirred on a magnetic stirrer at a speed of 300 rpm for a reaction time of 6 hours. After the reaction was completed, dialyze in deionized water for 36 h to remove unreacted glutathione and sodium lauryl sulfate. Quantitatively dilute the pure reduced albumin molecular deionized water to a certain concentration, and then half-d...

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Abstract

The invention belongs to the technical field of biomedical engineering nano medicaments and discloses a preparation method of a novel albumin nano medicament under a mild condition of 37 DEG C. The preparation method comprises the following steps of: 1) preparing an albumin aqueous solution; 2) preparing a reducing agent solution, adding the reducing agent solution into the albumin aqueous solution, adding a protein denaturing agent solution, and reacting for 0.5-6 hours at the temperature of between 30 and 80 DEG C to obtain a reduced albumin solution; 3) dialyzing or ultra-filtering the reduced albumin solution, and removing unreacted reducing agent and protein denaturing agent to obtain a reduced albumin nano solution; 4) mixing the reduced albumin nano solution with an acidic buffer solution to enable the pH value to be between 2.8 and 5.0, placing the mixture in an environment of 37 DEG C, stirring to obtain albumin nano particles, dialyzing, and freeze-drying to obtain the finalalbumin nano medicament. The albumin nanoparticles have very good serum stability and storage stability, stably exists in a body circulation system, increases the half-life of the medicament, and havereduction sensitivity characteristics.

Description

technical field [0001] The invention belongs to the technical field of biomedical engineering nano-medicine, and in particular relates to a preparation method of novel albumin nano-medicine under a mild condition of 37°C. Background technique [0002] Serum albumin is the most abundant protein in the plasma of living organisms. It undertakes various storage and transportation tasks in the body. It has multiple drug binding sites and is a natural carrier for the delivery of hydrophobic molecules in vivo. Nano-drug carriers prepared from serum albumin can significantly increase the solubility of hydrophobic compounds and improve the pharmacokinetics of drugs. Albumin nanocarriers are excellent drug delivery carriers due to their high drug loading capacity, low toxicity and side effects, and certain enrichment capabilities in tissues such as inflammation and tumors. Albumin has the characteristics of biodegradability, non-toxicity, non-antigenicity, patient tolerance and high ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42
Inventor 王坤胡风波
Owner 四川载荧生物科技有限公司
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