Responsive NO nano-drug as well as preparation method and application thereof

A nano-drug and drug technology, applied to nano-materials for the treatment of glaucoma, its preparation, in the field of responsive nitric oxide nano-drugs, can solve the problems of poor solubility and stability, low NO storage, limiting preclinical research and applications, and the like, To achieve the effect of convenient operation, simple preparation process and good application prospect

Active Publication Date: 2021-06-01
EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, JS-K has poor solubility and stability, and low NO storag

Method used

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  • Responsive NO nano-drug as well as preparation method and application thereof
  • Responsive NO nano-drug as well as preparation method and application thereof
  • Responsive NO nano-drug as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Nanomedicine HOS-J R preparation of

[0052] (a) Preparation of solid silica nanoparticles (MS): After stirring an aqueous solution of 2 g cetyltrimethylammonium chloride (CTAC) and 0.1 g triethanolamine (TEA) in a water bath at 95 °C, add 1 mL dropwise Tetraethyl orthosilicate (TEOS), react for 1h.

[0053] (b) Preparation of mesoporous silicone-coated solid nanoparticles (MS@MOS): adding bis-[r-(triethoxysilyl)propyl]-tetrasulfide (BTES) and TEOS to the above solution Mix the silicon source and react for 4h to obtain MS@MOS.

[0054] (c) Preparation of HOS: The above product was centrifuged, washed with ethanol, dispersed in a mixed solution of 100 mL ethanol and 10 mL concentrated hydrochloric acid (37%), and heated to 78° C. for 12 h to remove template CTAC. Repeat the above steps 3 times. After washing, redisperse in 20mL of water. Take 1 mL of the above solution and add 0.4 mL of ammonia water to react at 95°C for 3 h, selectively etch the MS core,...

Embodiment 2

[0057] Example 2: Cytotoxicity Evaluation

[0058] HOS-J R Nanomedicine plays a role by reaching the target cells trabecular meshwork cells and Schlemm canal endothelial cells that regulate intraocular pressure, so the first evaluation of HOS-J R Effect on HTM cell viability. HTM cells were seeded into 96-well cell culture plates at a density of 5000 cells per well. After overnight incubation at 37° C., the cells were washed with PBS, and then 100 ul of fresh cell culture medium containing different concentrations (0.15 and 0.3 mg / mL) of drugs was added thereto and incubated for 6 h, 12 h and 24 h. After each time point was reached, 10 ul of CCK-8 solution (10%) was added to continue incubation for 1 hour. Use a microplate reader to measure the absorbance at 450nm. Set up a blank group (no inoculation of cells), a control group (cells plus a medium without drugs) and an experimental group (cells plus a medium containing drugs) in the experiment, and calculate the experiment...

Embodiment 3

[0060] Embodiment 3: Pharmacological experiment

[0061] The intraocular pressure was measured at the same time period, and the mice were awake, using a Finnish animal-specific tonometer (model: tonolab) tonometer. When measuring the intraocular pressure, lightly grasp the skin of the neck behind the ear of the mouse with the left hand, make the mouse lie on the cage cover in a relaxed manner, and measure the intraocular pressure with the tonometer in the right hand. Measure three times and take the average value as an intraocular pressure measurement. Animal experiments were performed in accordance with the animal use and care system approved by the Animal Care and Use Committee of the Clinical Center of the National Institutes of Health. A mouse model of ocular hypertension - NOS3 knockout (NOS3 KO) mice was used in the experiments. NOS3 KO mice lack the NOS3 gene, resulting in loss of expression of the NO-producing endothelial nitric oxide synthase (eNOS) protein. Studie...

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Abstract

The invention provides a responsive nitric oxide (NO) nano-drug, which is characterized in that hollow mesoporous organic silicon nano-particles (HOS) are used as a carrier material to load a NO donor O2-(2, 4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazine-1-yl] azo-1-onium-1, 2-diol (JS-K). The invention further provides a preparation method and the application of the responsive NO nano-drug. The responsive NO nano-drug can be activated to slowly release NO in an anterior segment oxidation-reduction environment, so that the effect of reducing intraocular pressure is achieved. The preparation technology is simple, operation is convenient, complex and expensive equipment is not needed, industrial production is easy to achieve, and therefore the preparation method has good application prospects in the field of glaucoma treatment.

Description

technical field [0001] The invention relates to the field of medical nano-materials, in particular to a nano-material for treating glaucoma, in particular to a responsive nitric oxide (NO) nano-medicine, its preparation method and application. Background technique [0002] Glaucoma is a complex genetically heterogeneous disease in which pathologically elevated intraocular pressure is the most important risk factor. The most effective clinical treatment for glaucoma is by lowering intraocular pressure. The intraocular pressure is maintained by the production and outflow of aqueous humor, which is secreted by the ciliary body epithelial cells, and the outflow is mainly through the classical aqueous humor outflow pathway, and partly through the non-classical aqueous humor outflow pathway. Most of the IOP-lowering drugs currently used clinically achieve the purpose of lowering IOP by increasing the outflow of aqueous humor through non-classical pathways. The advantage of nitri...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K31/655A61P27/06
CPCA61K47/6923A61K47/6949A61K31/655A61P27/06
Inventor 宋毛毛雷苑范文培孙兴怀卢奕陈小元
Owner EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV
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