Magnetic targeting cell membrane modified ligand, drug-loading material, preparation method of magnetic targeting cell membrane modified ligand and drug-loading material and application of drug-loading material

A magnetic targeting and cell membrane technology, applied in pharmaceutical formulations, organic chemical methods, chemical instruments and methods, etc., can solve problems such as drug loading rate circulatory system stability defects, and achieve improved stability, drug loading rate, and stability Good, high cell uptake effect

Active Publication Date: 2020-11-17
SOUTHEAST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current biomimetic nano drug-loading materials based on cell membranes mainly realize the surface modification of nanoparticles and drug loading through physical coating, so there are obvious defects in drug loading rate and circulatory system stability.
In addition, this method of directly combining cell membranes with nanoparticles requires the drug delivery system to be enriched in tumor tissue first, and then its targeted uptake can be enhanced through the homologous homing effect, while the existing cell membrane nano drug-loading materials are often unable to Achieve rapid enrichment at tumor sites

Method used

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  • Magnetic targeting cell membrane modified ligand, drug-loading material, preparation method of magnetic targeting cell membrane modified ligand and drug-loading material and application of drug-loading material
  • Magnetic targeting cell membrane modified ligand, drug-loading material, preparation method of magnetic targeting cell membrane modified ligand and drug-loading material and application of drug-loading material
  • Magnetic targeting cell membrane modified ligand, drug-loading material, preparation method of magnetic targeting cell membrane modified ligand and drug-loading material and application of drug-loading material

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Preparation of intermediate 2

[0055] Compound 1 (6.0g, 14.1mmol) was dissolved in DCM / DMF (100 / 6mL), then DCC (3.5g, 16.8mmol) was added and stirred for 15min to obtain a mixed solution; then propargylamine (0.9g, 16.8mmol) Dissolve in 25mL DCM, then slowly drop into the above mixture, react at room temperature for 1h. After the reaction was complete, 5.9 g of a white solid (compound 2) was obtained by beating and suction filtration, with a yield of 92%. The intermediate was directly put into the next reaction without purification.

Embodiment 2

[0057] Preparation of intermediate 3

[0058] Dissolve the compound 2 (3.1g, 6.7mmol) prepared in the previous step in DMF (30mL), add piperidine (574.6mg, 6.7mmol) and react at room temperature for 0.5h, point the plate to observe the reaction progress, after the reaction is complete, add EA (ethyl acetate) (300mL) was washed three times with saturated sodium chloride solution, and the EA layer was dried with anhydrous sodium sulfate and concentrated column chromatography (DCM:MeOH=15:1) to obtain a light yellow solid (compound 3) 1.5 g, yield 73%.

[0059] 1 H NMR(600MHz,DMSO)δ8.32(s,1H),6.84(d,J=7.9Hz,2H),3.85(s,2H),3.11(s,1H),2.68(t,J=6.1Hz ,2H),2.50(m,2H),1.58(s,1H),1.38(s,9H).

[0060] ESI-MS:242.1[M+H] + .

Embodiment 3

[0062] Preparation of Intermediate 5

[0063] 4-(diethylamino) salicylaldehyde (5.0g, 25.9mmol) was dissolved in EtOH (100mL), then diethyl malonate (5.5g, 34.5mmol) was dissolved in 50mL EtOH, and slowly dropped into In the EtOH solution of the above-mentioned 4-(diethylamino)salicylaldehyde. Add piperidine (1.8g, 20.7mmol) and react at 90°C for 2h. After the reaction was complete, EtOH was removed under reduced pressure to obtain a mixture containing compound 4. The above mixture was hydrolyzed by adding NaOH solution, finally acidified with citric acid and extracted with ethyl acetate, and the ethyl acetate layer was spin-dried to obtain 6.0 g of a yellow solid (Compound 5), with a yield of 89%.

[0064] 1 H NMR(600MHz,DMSO)δ12.52(s,1H),8.59(s,1H),7.64(d,J=6.0Hz,1H),6.79(dd,J=9.0,1.6Hz,1H),6.57 (s,1H),3.48(q,J=7.0Hz,4H),1.13(t,J=7.0Hz,6H).

[0065] ESI-MS:260.3[M-H] - .

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Abstract

The invention discloses a magnetic targeting cell membrane modified ligand, a drug-loading material, a preparation method of the magnetic targeting cell membrane modified ligand and the drug-loading material and an application of the drug-loading material. The structural general formula of the magnetic targeting cell membrane modified ligand is shown as I series or II series in the formula (1). The magnetic targeting cell membrane drug-loading material is obtained by performing chemical covalent bond modification on a cell membrane to modify the magnetic targeting cell membrane modified ligand, an in-vitro test shows that the material is good in stability, can be effectively taken in by tumor cells, and has relatively high selectivity on the tumor cells, and besides, the material has remarkable paramagnetism. Under the condition of an external magnetic field, a magnetic targeting effect can be achieved. In an in-vitro anti-tumor test, the drug-loading material is remarkable in anti-tumor activity and hardly has toxicity to normal cells, so that the drug-loading material has a potential application of targeted therapy of malignant tumors.

Description

technical field [0001] The invention relates to medicinal chemistry, in particular to a magnetic targeting cell membrane modification ligand, a magnetic targeting cell membrane drug loading material and a preparation method and application thereof. Background technique [0002] In recent years, new biomimetic nano-drug-loaded materials have been paid more and more attention by researchers because of their obvious advantages in biocompatibility and avoiding immune system recognition. academic material. By fusing the cell membrane, especially the tumor cell membrane, on the surface of the nanoparticle, the nanoparticle can have the complex and unique surface physical and chemical properties of the original cell, for example, the adhesion molecules (such as vinculin, integrin, etc.) on the surface of the cancer cell membrane endow it with homologous recognition Therefore, cancer cell membranes are often used as coatings on the surface of spherical nanoparticles to enhance the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/517A61K31/555A61K41/00A61K47/52A61K47/54A61K49/00A61P35/00C07D405/14C07D409/14C07F15/00
CPCA61K47/6901A61K47/545A61K47/52A61K41/00A61K31/517A61K31/555A61K49/0039A61K49/0052A61K49/0097A61P35/00C07D409/14C07D405/14C07F15/0093C07B2200/11A61K2300/00Y02P20/55
Inventor 房雷刘敦瑞罗燕丽李择瑞
Owner SOUTHEAST UNIV
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