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A kind of pharmaceutical composition and its preparation method and application

A composition and drug technology, applied in the direction of drug combination, pharmaceutical formula, boron compound active ingredients, etc., can solve the problems of poor stability, low bioavailability, high normal tissue toxicity, etc., and achieve narrow distribution and high drug loading capacity Effect

Active Publication Date: 2017-09-15
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the clinical use and efficacy of bortezomib paclitaxel are severely limited by poor water solubility, poor stability, low bioavailability, and high toxicity to normal tissues

Method used

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  • A kind of pharmaceutical composition and its preparation method and application
  • A kind of pharmaceutical composition and its preparation method and application
  • A kind of pharmaceutical composition and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0040] Example 1-1: Synthesis of PEI-PA

[0041]Synthesis of PEI-PA: Weigh 256 mg of dry palmitic acid, pour it into a three-necked flask, add 15 mL of dimethylformamide (DMF), completely dissolve the palmitic acid, and then weigh 380 mg of HATU (2-(7- Nitrobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate) was added to the DMF solution of palmitic acid, and 129μL DIEA(N,N- diisopropylethylamine), reacted overnight under magnetic stirring. Weighed 250mg PEI and dissolved it in 15mL DMF. After complete dissolution, the activated palmitic acid mixed solution was added dropwise to the PEI solution, and reacted for 12 hours to obtain the PEI-PA polymer.

Embodiment 1-2

[0042] Example 1-2: Synthesis of PEI-PA

[0043] Synthesis of PEI-PA: Weigh 256 mg of dry palmitic acid, pour it into a three-necked flask, add 15 mL of dimethylformamide (DMF), completely dissolve the palmitic acid, then weigh 570 mg of HATU (2-(7- Nitrobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate) was added to the DMF solution of palmitic acid, and 104μL DIEA(N,N- Diisopropylethylamine), reacted under magnetic stirring for 6 hours. Weighed 500mg PEI and dissolved it in 15mL DMF. After complete dissolution, the activated palmitic acid mixed solution was added dropwise to the PEI solution and reacted for 24 hours to obtain the PEI-PA polymer.

Embodiment 1-3

[0044] Example 1-3: Synthesis of PEI-PA

[0045] Synthesis of PEI-PA: Weigh 256 mg of dry palmitic acid, pour it into a three-necked flask, add 15 mL of dimethylformamide (DMF), completely dissolve the palmitic acid, then weigh 304 mg of HATU (2-(7- Nitrobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate) was added to the DMF solution of palmitic acid, and 194μL DIEA(N,N- Diisopropylethylamine), reacted for 20 hours under magnetic stirring. 130mg PEI was weighed and dissolved in 15mL DMF. After complete dissolution, the activated palmitic acid mixed solution was added dropwise to the PEI solution and reacted for 8 hours to obtain the PEI-PA polymer.

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Abstract

The invention relates to a pharmaceutical composition which comprises a carrier and a drug loaded on the carrier, wherein the drug is bortezomib and taxol and the carrier is a polyethyleneimine-palmitic acid (PEI-PA) polymer. The preparation method of the pharmaceutical composition comprises the following steps: carrying out amidation reaction on hyperbranched polyethyleneimine and palmitic acid to obtain the PEI-PA polymer, wherein the number-average molecular weight of the polyethyleneimine is 5000-100000; and dissolving the PEI-PA polymer, bortezomib and taxol in an organic solvent which is insoluble in water, adding an aqueous solution of a surfactant, mixing, carrying out ultrasonic treatment, removing the organic solvent at a reduced pressure, and centrifugally washing to obtain the pharmaceutical composition. The pharmaceutical composition provided by the invention can be used for preparing a tumor cell inhibitor.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a pharmaceutical composition and its preparation method and application. Background technique [0002] The self-assembled core-shell structure of the amphiphilic copolymer in aqueous solution can increase the solubility of hydrophobic drugs to a certain extent, stabilize the drug, prolong the residence time of the drug in the body, and reduce the side effects of the drug on the human body. In the past ten years, the nanoparticle drug delivery system composed of amphiphilic polymer materials has received extensive attention from the international medical community and has been applied in gene medicine, biological diagnosis, anti-transfection drugs and drug controlled release systems. [0003] As a drug carrier, polyethyleneimine (PEI) has certain toxicity, and the toxicity depends on the molecular weight. The larger the molecular weight, the greater the cytotoxicity. A feasi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/69A61K38/05A61K47/34A61P35/00A61K31/337
CPCA61K31/337A61K31/69A61K38/05A61K47/34A61K2300/00
Inventor 吴雁张瑞锐苏世帅刘英华
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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