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Nano-drug carrier, nano-drug preparation, preparation method and application

A nano-drug carrier and nano-preparation technology, applied in biochemical equipment and methods, drug combination, drug delivery, etc., can solve the problem that the drug loading and encapsulation efficiency of polymer carriers cannot meet clinical needs, and achieve no immunogen Sexuality, reduced number of administrations, and high stability

Pending Publication Date: 2021-01-15
HUBEI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, compared with viral vectors, the drug loading and encapsulation efficiency of existing polymer carriers cannot meet the existing clinical needs, and there is still a long way to go before the actual clinical application

Method used

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  • Nano-drug carrier, nano-drug preparation, preparation method and application
  • Nano-drug carrier, nano-drug preparation, preparation method and application
  • Nano-drug carrier, nano-drug preparation, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] The hydrophobic oleic acid is connected to the side chain carboxyl group of branched polyethyleneimine (molecular weight 600Da) through amide reaction to prepare polyethyleneimine-oleic acid coupling (polyethyleneimine-oleic acid) with a modification degree of 10.4 %.

[0054] Dissolve 2mg of silibinin, 5mg of polyethyleneimine-oleic acid and 30mg of Solutol HS15 (stabilizer) in methanol in a round-bottomed flask, rotary evaporate to form a film, add 5% glucose solution for hydration, and obtain polyethylene Imine-oleic acid drug-loaded nano-preparation ( figure 1 , 2 Among them, nanoformulation particles 1). Add polyethyleneimine-oleic acid drug-loaded nano-preparation to dissolve 1mg / mL silibinin-collagenase to obtain figure 1 with 2 Nanoformulation Particles 2. Finally, the nano-preparation particle 2 is added in the 5% glucose solution of 1mg / mL chondroitin sulfate, stirred for 5min to obtain the nano-preparation of silibinin-collagenase (such as figure 1 with...

Embodiment 2

[0057]Hydrophobic stearic acid is connected to side chain carboxyl group of branched polyethyleneimine (molecular weight: 1.8kDa) through amide reaction to prepare polyethyleneimine-stearic acid coupling product with a modification degree of 6.2%. Dissolve 5mg of polyethyleneimine-stearic acid, 35mg of Solutol HS15, 2mg of DSPE-PEG2000 and 1mg of paclitaxel (small molecule drug) in ethanol in a round-bottomed flask, rotary evaporate to form a film, add normal saline to hydrate, and obtain Polyethyleneimine-stearic acid drug-loaded nanoformulations. Among them, Solutol HS15 and DSPE-PEG2000 are stabilizers.

[0058] The polyethylenimine-stearic acid drug-loaded nano-preparation was sequentially added to the solution containing 50 μg / mL CpG (nucleic acid drug), 500 μg / mL ovalbumin (protein drug) and 2 mg / mL folic acid-polyethylene glycol conjugate (Targeting functional molecules) in physiological saline, stirred for 10 minutes to obtain a three-drug-loaded nano-preparation with...

Embodiment 3

[0060] By amide reaction, hexadecanoic acid is connected to the side chain carboxyl group of linear polyethyleneimine (molecular weight is 25kDa), and the polyethyleneimine-hexadecanoic acid coupling product (polyethyleneimine-hexadecanoic acid) is prepared. The degree of modification is 7.1%.

[0061] Dissolve 4 mg polyethyleneimine-hexadecanoic acid, 30 mg poloxamer 188 (stabilizer) and 1 mg doxorubicin (small molecule drug) in methanol and place in a round-bottomed flask, rotary evaporate to form a film, add amino acid The solution is hydrated to obtain the polyethyleneimine-hexadecanoic acid drug-loaded nano-preparation. The polyethyleneimine-hexadecanoic acid drug-loaded nano-preparation was successively added to the phosphate buffer solution (aqueous solvent) dissolved with 1 mg / mL ovalbumin (protein drug) and folate (targeting functional molecule) , and stirred for 5 minutes to obtain a double drug-loaded nano-preparation with a particle size of 50nm.

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Abstract

The invention relates to a nano-drug carrier, which comprises a polyethyleneimine derivative, wherein the fatty acid modification degree of the polyethyleneimine derivative is 0.1-12%, and the biological molecular weight range of the polyethyleneimine derivative is 0-25kDa. The invention also discloses a nano-drug preparation prepared from the nano-drug carrier, a preparation method and application. The nano-drug carrier provided by the invention has the advantages of high drug loading capacity, high encapsulation efficiency, good biocompatibility and the like, is safe and nontoxic, is free from immunogenicity and is biodegradable, a drug treatment dosage is greatly reduced, in addition, the nano-drug carrier can slowly release drugs on a targeting position so as to perform a curative effect for a long time, drug administration frequencies are greatly reduced, and therefore, a toxic and side effect of the drug is further lowered.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to nano drug carriers, nano drug preparations, preparation methods and applications. Background technique [0002] Small molecule drugs play an important and irreplaceable role in human health. They have the advantages of small molecular weight, clear physical and chemical properties, simple structure, good stability, low price, and no antigenicity. However, there are also some problems. There are obvious peaks and troughs in the blood concentration of small molecule drugs after administration, making them more toxic and side effects and reducing drug efficacy; for chronic diseases, long-term continuous administration is required, which increases the physical, psychological and economic burden of patients. [0003] Compared with small molecule chemical drugs, protein peptide drugs have higher pharmacological activity, stronger pertinence, and lower toxicity. Ther...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/59A61K47/54A61K47/61A61K47/60A61K47/69A61K31/357A61K38/48A61K31/337A61K38/38A61K31/7105A61K31/704A61K45/06A61P35/00
CPCA61K47/59A61K47/542A61K47/61A61K47/545A61K47/60A61K47/6935A61K47/6939A61K31/357A61K38/4886A61K31/337A61K38/38A61K31/7105A61K31/704A61K45/06A61P35/00C12Y304/24
Inventor 罗静雯马立新董衍明张志威
Owner HUBEI UNIV
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