Sialic acid nanoparticle as well as preparation method and application thereof

A nanoparticle and sialic acid technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of reducing clearance, changing viscosity, and poor patient dependence

Pending Publication Date: 2021-05-04
XIAMEN NUOKANGDE BIOLOGICAL TECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004]However, the application of sialic acid nasal spray is limited in dose, and sialic acid is easily cleared by mucus and nasal mucosal cilia.
The sialic acid nasal administration preparation of Chinese patent application CN 11544379 A combines sialic acid with phospholipids in the form of a "complex". On the one hand, phospholipids are used to reduce the viscosity of nasal mucus, thereby reducing the removal of sialic acid by nasal mucus; On the one hand, the amphiphilicity of phospholipids is used to connect the hydrophobic end with the fat-soluble nasal mucosa, and the hydrophilic end is connected with the free sialic acid in the drug, so that the sialic acid is closely attached to the surface of the nasal mucosal cells and prolongs the sialic acid in the nasal mucosa. residence time, but the sialic acid nasal administration preparation prepared by this method will change the normal nasal mucus viscosity, and the smell is not friendly, and the patient dependence is poor

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  • Sialic acid nanoparticle as well as preparation method and application thereof
  • Sialic acid nanoparticle as well as preparation method and application thereof
  • Sialic acid nanoparticle as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] The preparation of embodiment 1 sialic acid nanoparticles

[0039] Take 750 mg of polystyrene maleic anhydride copolymer (PMSA) with a molecular weight of 10000 and dissolve it in 10 mL of DMF, then add 350 mg of aminosialic acid (SA, x=2), and add 0.8 mL of triethylamine to the above In the reaction solution, stir the reaction at room temperature for 12 hours, then add 8 mL of saturated NaHCO 3 Aqueous solution, the reaction solution can be collected after stirring at room temperature for 1 hour; when collecting the reaction solution, use a dialysis bag with a molecular weight cut-off of 10,000 for dialysis for 24 hours, the dialysate is ultrapure water, and the medium is changed 4-5 times. Finally, the solid substance obtained by freeze-drying the solution in the dialysis bag is the sialic acid polymer compound.

[0040] 10 mg of the above-mentioned sialic acid polymer compound was dissolved in 10 ml of ultrapure water, and ultrasonic (40 KHz, 25° C.) was used for 1 ...

Embodiment 2

[0042] The preparation of embodiment 2 sialic acid nanoparticles

[0043]Take 1000 mg of polystyrene-maleic anhydride copolymer (PMSA) with a molecular weight of 5000 and dissolve it in 10 mL of DMF, then add 500 mg of aminosialic acid (SA, x=4), and add 0.5 mL of triethylamine to the above In the reaction solution, stir the reaction at room temperature for 12 hours, then add 10 mL of saturated NaHCO 3 Aqueous solution, the reaction solution can be collected after stirring at room temperature for 1 hour; when collecting the reaction solution, use a dialysis bag with a molecular weight cut-off of 5000 for dialysis for 24 hours, the dialysate is ultrapure water, and the medium is changed 4-5 times. Finally, the solid substance obtained by freeze-drying the solution in the dialysis bag is the sialic acid polymer compound.

[0044] 10 mg of the above-mentioned sialic acid polymer compound was dissolved in 10 ml of ultrapure water, and ultrasonic (40 KHz, 25° C.) was used for 1 ho...

Embodiment 3

[0046] The preparation of embodiment 3 sialic acid nanoparticles

[0047] Take 500 mg of polystyrene-maleic anhydride copolymer (PMSA) with a molecular weight of 20,000 and dissolve it in 10 mL of DMF, then add 200 mg of aminosialic acid (SA, x=4), and add 1 mL of triethylamine to the above reaction solution, stirred at room temperature for 12 hours, then added 10 mL of saturated NaHCO 3 Aqueous solution, the reaction solution can be collected after stirring at room temperature for 1 hour; when collecting the reaction solution, use a dialysis bag with a molecular weight cut-off of 20,000 for dialysis for 24 hours, the dialysate is ultrapure water, and the medium is changed 4-5 times. Finally, the solid substance obtained by freeze-drying the solution in the dialysis bag is the sialic acid polymer compound.

[0048] 10 mg of the above-mentioned sialic acid polymer compound was dissolved in 10 ml of ultrapure water, and ultrasonic (40 KHz, 25° C.) was used for 1 hour to obtain ...

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Abstract

The invention relates to a sialic acid nanoparticle and a preparation method and application thereof. The sialic acid nanoparticle is prepared through the steps that a polystyrene maleic anhydride copolymer serves as a framework, aminated sialic acid reacts with acid anhydride groups on macromolecules, sialic acid is covalently connected to a macromolecule framework, and the obtained macromolecule object is subjected to ultrasonic treatment in an aqueous solution to obtain the sialic acid nanoparticle. A nasal spray prepared from the sialic acid nanoparticle has an adhesion effect on mucous membrane tissues, so that sialic acid is not easily removed by nasal cilia, the residence time of the sialic acid in the nasal cavity is prolonged, the invasion of influenza virus, parainfluenza virus, respiratory syncytial virus and other viruses taking cell surface sialic acid as a receptor is blocked, and lasting protection is provided for the respiratory tract. The risk of viral infection is reduced, the prepared nasal spray preparation is safe, has no toxic or side effect, has no peculiar smell, and does not change the normal nasal mucus viscosity.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a sialic acid nanoparticle and its preparation method and application. Background technique [0002] Sialic acid (SA) is a natural carbohydrate compound that widely exists in biological systems. It is a general term for a family of derivatives based on the nine-carbon sugar neuraminic acid. There are more than 50 species, which are widely present in the cell membrane glycoprotein and lipoproteins, and play an important role in many important processes of life, participating in cell recognition, survival, reproduction, biomembrane flow, and endocytosis. [0003] Respiratory viruses such as influenza are mainly transmitted through the air, invade the human body through the mouth and nose, and use cell surface sialic acid as a ligand for adhesion and infection. Therefore, blocking the binding of the virus to the cell surface sialic acid ligand can block virus inv...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K9/12A61K47/58A61K31/7012A61P31/16
CPCA61K9/5138A61K9/0043A61K9/12A61K47/58A61K31/7012A61P31/16
Inventor李柱田云鹏赵绍军
OwnerXIAMEN NUOKANGDE BIOLOGICAL TECH CO LTD