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Preparation method and application of fluorescence nanometer diamond-doxycycline compound

A technology of fluorescent nanometer and nanodiamond, which is applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, drug combinations, etc. It can solve the problems of reduced drug efficacy, structural damage of doxorubicin, photobleaching, etc. , to achieve stable chemical properties, reduce toxic side effects, and good biocompatibility

Inactive Publication Date: 2013-08-14
SHANXI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In 2007, the team led by Dr. Dean Ho, an American scientist, used nano-diamonds (2-8nm) that do not emit fluorescent signals to load doxorubicin under NaCl conditions, and in 2011 under the conditions of sodium hydroxide concentration of 2.5mM (pH about 11.4) The nano-diamond-loaded doxorubicin was prepared under the condition of pH ≥ 11.0, and the structure of doxorubicin was destroyed, and the drug effect may be reduced.
In addition, since the team led by Dr. Dean Ho used non-luminescent nano-diamonds, fluorescent dyes were required to mark the distribution of nanoparticles in the body. Track the activity of labeled materials in cells or in vivo

Method used

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  • Preparation method and application of fluorescence nanometer diamond-doxycycline compound

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Embodiment 1

[0019] Embodiment 1: the preparation of nanodiamond-doxorubicin complex

[0020] Weigh 2.0 mg of fluorescent nanodiamonds, add 1 mL of NaOH solution at pH 10.0, sonicate at 100 W for 30 min, then add 80 μL of 2 mg / mL doxorubicin at pH 10.0 to make the mass reach 160 μg, sonicate at 100 W for 10 min, place on a shaker The homogenizer is fully shaken, its rotation speed is 18rpm, and the shaking time is 3h. After the reaction, centrifuge at 15,000 rpm with a high-speed centrifuge for 5 minutes. The supernatant was placed in a 5mL centrifuge tube, the precipitate was washed with NaOH solution of pH 10.0 for 2 times, and the supernatant was placed in the first 5mL centrifuge tube. The absorbance at the 490nm peak position of doxorubicin was detected by means of ultraviolet-visible spectroscopy, and the adsorption amount of DOX was calculated. After calculation, the adsorption of doxorubicin per mg of diamond was about 69 micrograms (69 μg / mg).

Embodiment 2

[0022] Weigh 2.0 mg of fluorescent nanodiamonds, add 2 mL of NaOH solution at pH 10.0, sonicate at 100 W for 30 min, then add 90 μL of 2 mg / mL doxorubicin at pH 10.0 to make the mass reach 180 μg, sonicate at 100 W for 10 min, place on a shaker The homogenizer is fully shaken, its rotation speed is 18rpm, and the shaking time is 3h. After the reaction, centrifuge at 15,000 rpm with a high-speed centrifuge for 5 minutes. The supernatant was placed in a 5mL centrifuge tube, the precipitate was washed with NaOH solution of pH 10.0 for 2 times, and the supernatant was placed in the first 5mL centrifuge tube. The absorbance at the 490nm peak position of doxorubicin was detected by means of ultraviolet-visible spectroscopy, and the adsorption amount of DOX was calculated. It was calculated that about 70 micrograms (70 μg / mg) of doxorubicin were adsorbed per mg of diamond.

Embodiment 3

[0024] Weigh 2.0 mg of fluorescent nanodiamonds, add 1 mL of NaOH solution with pH 10.0, sonicate at 100 W for 30 min, then add 100 μL of 2 mg / mL doxorubicin at pH 10.0 to make the mass reach 200 μg, sonicate at 100 W for 10 min, place in a shaker The homogenizer is fully shaken, its rotation speed is 18rpm, and the shaking time is 3h. After the reaction, centrifuge at 15,000 rpm with a high-speed centrifuge for 5 minutes. The supernatant was placed in a 5mL centrifuge tube, the precipitate was washed with NaOH solution of pH 10.0 for 2 times, and the supernatant was placed in the first 5mL centrifuge tube. The absorbance at the 490nm peak position of doxorubicin was detected by means of ultraviolet-visible spectroscopy, and the adsorption amount of DOX was calculated. It was calculated that about 70 micrograms (70 μg / mg) of doxorubicin were adsorbed per mg of diamond.

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Abstract

The invention provides a fluorescence nanometer diamond-doxycycline (FND-DOX) compound, which is prepared from red fluorescence nanometer diamond as carriers under the condition that pH is 10.0 by using physical adsorption doxycycline loading, and the particle size is 197+ / -1.8nm. The compound acts with the human liver cancer cells (HepG2), and results show that the FND-DOX has the medicine slow release characteristics. In addition, the structural characteristics of a capillary system in tumor tissues can be utilized, i.e. the EPR (electron paramagnetic resonance) effect is utilized, so the FND-DOX is captured by the tumor parts (i.e. the passive targeted effect is realized). Therefore, the toxic or side effect of chemotherapy medicine on normal cells can be reduced, and in addition, the lethality on the tumor cells can also be improved. The FND-DOX can be applied to the preparation of antitumor medicine.

Description

technical field [0001] The invention relates to a drug-loaded nanoparticle, specifically using fluorescent nano-diamond as a carrier to prepare a fluorescent nano-diamond-doxorubicin complex (FND-DOX) and its application in the preparation of antitumor drugs through condition optimization. Background technique [0002] The anti-tumor drugs of traditional chemotherapy will inevitably bring toxic side effects due to the lack of selectivity to tumor cells, that is, no drug-guiding effect. While killing tumor cells, normal cells are also damaged, causing great harm to patients and greatly affecting the quality of life and therapeutic effect of patients. Therefore, in clinical practice, controlling drug delivery and drug release is an urgent problem to be solved in chemotherapy. In response to this subject, natural biodegradable polymer materials such as serum albumin, hemoglobin collagen, and gelatin were used earlier. It has good biocompatibility, but it is difficult to prepa...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/704A61K47/04A61P35/00
Inventor 李英奇苏刚仝姚莉
Owner SHANXI UNIV
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