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A kind of nano drug carrier, drug carrier system and preparation method for ultrasonic controlled release based on pullulan

A nano-drug carrier, pullulan polysaccharide technology, applied in non-active ingredients medical preparations, active ingredients-containing medical preparations, drug combinations, etc., can solve drug resistance, reduce the therapeutic effect of cancer cells, tumors Cells can not reach the drug concentration and other problems, to achieve the effect of good water solubility and low viscosity

Active Publication Date: 2019-10-11
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these drug carriers generally release the drug slowly through diffusion or hydrolysis, resulting in the failure of effective drug concentration in tumor cells, reducing the therapeutic effect and causing drug resistance of cancer cells

Method used

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  • A kind of nano drug carrier, drug carrier system and preparation method for ultrasonic controlled release based on pullulan
  • A kind of nano drug carrier, drug carrier system and preparation method for ultrasonic controlled release based on pullulan
  • A kind of nano drug carrier, drug carrier system and preparation method for ultrasonic controlled release based on pullulan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The preparation of embodiment 1 P-OC

[0048] (1) Under nitrogen protection, in a 50mL round bottom flask, HTEMPO (1.034g, 6mmoL) and triethylamine (0.83mL) were dissolved in 15mL of anhydrous dichloromethane and stirred in ice bath for 30min, then the stearin Acyl chloride (1.81mL, 6mmoL) was dissolved in 10mL of anhydrous dichloromethane, slowly added, and stirred at 30°C for 30h, the reaction mixture was poured into a separatory funnel, extracted with a large amount of deionized water, and unreacted HTEMPO was washed away. , take out the organic phase, dry with anhydrous magnesium sulfate, filter, and remove dichloromethane by rotary evaporation. The residue is separated from impurities by column chromatography, and eluted with a 9:1 eluent of petroleum ether and ethyl acetate to obtain a red The oily product, piperidinium stearate (abbreviated as OC), was stored in a refrigerator at 4°C.

[0049] (2) Under nitrogen protection, in a 100mL round bottom flask, put pul...

Embodiment 2

[0053] Example 2 Characterization of Proton Spectrum and High Resolution Mass Spectrometry

[0054] The OC prepared in Example 1 was dissolved in deuterated chloroform and P-Cl, P-OC, and P were dissolved in deuterated dimethyl sulfoxide or deuterated water, and the NMR ( 1 H NMR) for structural verification, and the OC prepared in Example 1 was dissolved in dichloromethane to further verify the structure by high-resolution mass spectrometry.

[0055] The result is as figure 1 Shown, piperidinium stearate (e, CDCl 3 ) in the spectrum, a proton peak appears at δ7.13ppm, which is a characteristic peak formed by the nitroxide free radical on piperidine combined with a proton, and a piperidine methine (-CH-O) proton peak appears at δ5.23ppm, and δ1.26ppm For the four methyl groups on piperidine (CH 3 ) peak, and methyl and methylene proton peaks appear on stearic acid at δ0.88ppm, consistent with its piperidine stearate cleavage peak. Simultaneously the high resolution mass sp...

Embodiment 3

[0056] Example 3 Preparation of P-OC / DOX drug-loaded nanomicelles

[0057] 20 mg of P-OC prepared in Example 1 was dissolved in 4 mL of DMSO, and a mixed solution formed by dissolving 2.1 mg of doxorubicin hydrochloride and 1.03 μL of triethylamine in 400 μL of DMSO was added (wherein, doxorubicin hydrochloride and triethylamine The molar ratio of doxorubicin is 1:2, the concentration of doxorubicin is 5mg / mL, the mixing mass ratio of doxorubicin and P-OC is 1:10), and stirred for 1h, dialyzed for 72h, and P-OC can be obtained after lyophilization / DOX drug-loaded nanomicelles.

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Abstract

The invention discloses a pullulan based nano-drug carrier used for ultrasonic control release, a drug carrier system and a preparation method of the nano-drug carrier, and belongs to the technical field of biomateirals. 4-chlorobutyryl chloride and stearic piperidine ester are modified on a side chain of the pullulan successively through the acylation reaction and the coupling reaction of the free radical of nitroxide to prepare P-OC. The invention further discloses application of the ultrasonic control release carrier system, the P-OC is self-assembled in a water soluble environment to forma micelle structure, a hydrophobic anti-cancer drug is wrapped on an inner core, and the drug is controllably delivered in the space and time. The drug-loaded nano-micelle P-OC / DOX has a better effecton killing the cancer cell under the external ultrasonic condition, the effect on inhibiting the cancer cell is poor without the ultrasonic treatment, and the ultrasonic controllable release drug carrier system has a potential application value in the fields of sustained release of the drug and the treatment of cancers.

Description

technical field [0001] The invention belongs to the technical field of biomaterials, and in particular relates to a pullulan-based nano drug carrier for ultrasonic controlled release, a drug carrier system and a preparation method. Background technique [0002] At present, cancer has become a serious threat to human health. The common methods for treating cancer include surgery, radiotherapy, and chemotherapy. Among them, chemotherapy is one of the important cancer treatment methods. However, due to its lack of Selectivity, fast metabolism in the body, short half-life, in order to achieve the effect of treating tumors, it is often used to increase the dose of administration, resulting in serious side effects on normal human tissues during the treatment process, such as nausea, vomiting, hair loss and other side effects. The clinical application of these anticancer drugs is greatly limited, so designing efficient drug delivery carriers is of great significance for the treatm...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/22A61K47/36A61K31/704A61P35/00
Inventor 王静云汪祥刘会莹包永明舒迅徐琳琳任盼星
Owner DALIAN UNIV OF TECH
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