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Radiation protection nano drug acting on small intestines and preparation method of radiation protection nano drug

A nano-drug and radiation protection technology, which is applied in drug combination, drug delivery, and pharmaceutical formulations, etc., can solve the problems of inability to exert high-efficiency radiation protection effects, and inability to resist the rapid flow of digestive juices, so as to improve time and utilization efficiency and reduce systemic Toxic and side effects, the effect of increasing the effective concentration

Active Publication Date: 2019-09-06
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most importantly, most drugs are unable to resist the rapid flow of digestive juices, so oral drugs are often difficult to stay in the small intestinal tissue with high radiation sensitivity, so they cannot exert an efficient radiation protection effect

Method used

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  • Radiation protection nano drug acting on small intestines and preparation method of radiation protection nano drug
  • Radiation protection nano drug acting on small intestines and preparation method of radiation protection nano drug
  • Radiation protection nano drug acting on small intestines and preparation method of radiation protection nano drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1 Synthetic nano-medicine

[0048] Arginine (0.867g, 4.977mmol) was dissolved in 40mL morpholineethanesulfonic acid solution (25mM, pH 5.0), and then N-hydroxysuccinimide (2.291g, 19.908mmol), 1-(3 -Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.816g, 19.908mmol) was activated for 2 hours, and then a chitosan solution (1.0g, 4.977mmol) was added to the above mixture, and after stirring at room temperature for 24 hours, sodium hydroxide (0.1M) was added to terminate the reaction. Then thalidomide (1.0mg / mL, 10mL) dissolved in water and acetonitrile mixture (v / v=1 / 1) was slowly dropped into the above polymer solution (10mg / mL, 100mL) and kept stirring The acetonitrile was removed by nitrogen gas overnight, and the supernatant was lyophilized after centrifugation. The lyophilized sample (20.0 mg) was transferred into a dopamine solution (2 mg / mL, 40 mL, pH 8.5), stirred at room temperature for 3 hours, washed with deionized water and centrifuged to ...

Embodiment 2

[0053] Example 2 In vitro radiation protection effect test

[0054] An appropriate amount of nanomedicine (11.237 μg / mL) prepared in Example 1 was dispersed in the small intestinal crypt organoid medium, and the small intestinal crypt organoids of C57BL / 6J mice were cultured in vitro, and 14 Gy dose of X Irradiation, for small intestinal crypts that disintegrate after radiation injury (eg Figure 5 A) and crypts with intact shape and sharp edges (such as Figure 5 B) perform calculations, Figure 5 As shown in C, the survival rate of crypts after irradiation with nanomedicine is about 42.67%, which is significantly higher than that of the control group (*p<0.05). The results show that the nanomedicine has a good radiation protection effect.

Embodiment 3

[0055] Example 3 Intestinal adhesion test

[0056] The radioprotective nanomedicine prepared in Example 1 was labeled with Cy5.5 fluorescent dye, and then resuspended in phosphate buffered saline. After C57BL / 6J mice were fasted for 12 hours, the dye-labeled nanomedicine solution (4mg / mL, 0.5mL) were given to mice in each group by intragastric administration. After the mice were euthanized 6 hours and 24 hours after administration, the small intestine tissue was taken for in vitro fluorescence imaging. The instrument used was a Kodak FX Pro in vivo fluorescence imaging system with an excitation light of 630 nm and an emission light of 700 nm.

[0057] Such as Image 6 As shown, 6 hours after administration ( Image 6 A), the mouse small intestine showed a strong fluorescent signal, indicating that most of the drug had accumulated in the small intestine. 24 hours after administration ( Image 6 B), the fluorescent signal in the mouse small intestine tissue still maintains ...

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Abstract

The invention relates to a construction method of a nano drug with small-intestine adhesiveness. The method includes: activating basic amino acid by a micromolecular catalyst, and adding into polysaccharide solution to obtain an amphiphilic macromolecular polymer through reaction; adding drug solution, and well mixing to obtain drug-loading nanoparticles, wherein each nanoparticle comprises a hydrophilic portion and a hydrophobic portion, each hydrophilic portion refers to basic amino acid, and each hydrophobic portion consists of polysaccharide and a drug with a radiation protection performance or an inhibiting effect on ionizing radiation induced apoptosis; adding the drug-loading nanoparticles into dopamine solution, and performing complete reaction to obtain the nano drug with basic amino acid and polydopamine on the surface. The oral nano drug with intestinal adhesiveness is high in biocompatibility and tolerant to gastrointestinal acid-base environments and has small-intestine adhesiveness and intestinal mucus barrier penetrating power.

Description

technical field [0001] The invention relates to a nano-medicine acting on the small intestine, in particular to a radiation-protecting nano-medicine acting on the small intestine and a preparation method thereof. Background technique [0002] With the development and wide application of nuclear industry and nuclear technology, the importance of nuclear safety has become increasingly prominent. How to effectively prevent acute radiation injury has become an important research content in the field of nuclear safety. If the body is exposed to ionizing radiation with a dose greater than 10Gy in a short period of time, it will cause severe gastrointestinal syndrome, which can cause symptoms such as diarrhea, bloody stool, and intestinal inflammation, and cause death within a few weeks. Although the existing radiation protection drugs can exert a certain radiation protection effect, their low targeting and serious side effects often lead to unsatisfactory treatment effects for int...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K9/14A61K47/36A61K47/34A61K9/00A61K45/00A61K31/454A61P1/00
CPCA61K9/5161A61K9/146A61K9/0053A61K45/00A61K31/454A61P1/00A61K9/5192
Inventor 华道本张钰烁王璐杨森
Owner SUZHOU UNIV
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