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CpG nucleic acid drug conveying system and making method thereof

A nucleic acid drug and delivery system technology, applied in the direction of drug combination, medical formula, genetic material components, etc., can solve the problems of uncontrollable release, immunogenic reaction, immune response, etc., to achieve increased storage capacity, improved inhibition and treatment, The effect of increasing secretion

Inactive Publication Date: 2014-11-05
UNIV OF SHANGHAI FOR SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The delivery system that carries CpG nucleic acid drugs through viruses has the highest delivery efficiency, but it will cause immunogenic reactions, and the viral vector itself is dangerous and expensive, which limits the use of the delivery system
Organic materials mainly include organic micelles, liposomes, biodegradable polymer materials, etc. However, due to the poor thermochemical stability of these materials, the release is uncontrollable, and there are also immune reactions, which make their applications subject to many restrictions.
Inorganic nanoparticles are a class of CpG nucleic acid drug carriers that have been studied more at present, such as calcium phosphate, boron nitride, silicon oxide, manganese oxide, etc. Although these inorganic nanoparticles are controllable in preparation, have low toxicity, and can be functionally modified, but Its CpG nucleic acid drug has a small carrying capacity and low delivery efficiency
[0006] It has been reported in the literature that SBA-15 mesoporous silica particles are used to deliver CpG nucleic acid drugs to 293XL-hTLR9 cells. Since SBA-15 mesoporous particles are short rods with a diameter of 500 nm and an aspect ratio of 2, the cells Mesoporous particles are more difficult to uptake, so the delivery efficiency of their CpG nucleic acid drug delivery system is lower

Method used

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  • CpG nucleic acid drug conveying system and making method thereof
  • CpG nucleic acid drug conveying system and making method thereof
  • CpG nucleic acid drug conveying system and making method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] The CpG nucleic acid drug delivery system provided in this example includes a carrier and a CpG nucleic acid drug stored in the carrier, the carrier is mesoporous silica nanoparticles modified with an aminoalkane coupling agent, and the CpG nucleic acid drug is a CpG oligodeoxynucleotides, namely:

[0032] 5'-TCAGAGAGTTAGAGAGTTAGAGAGTCAGAGAGTTAGAGAGTTAGAGAGTCAGAGGTTAGAGAGTTAGAGAG-3'.

[0033] The aminosilane coupling agent used in the preparation method of the CpG nucleic acid drug delivery system is γ-aminopropyltriethoxysilane, the silicon source used is ethyl orthosilicate, and the surfactant used is cetyl p- Tosylate, the cosolvent that adopts is triethanolamine, specifically comprises following three steps:

[0034]Step 1: Dissolve 3eq of cetyl p-toluenesulfonate (CTAT) and 5eq of triethanolamine (TEA) in 4000eq of deionized water at 80°C, stir for 1 hour to dissolve completely; then slowly add After 18eq of tetraethyl orthosilicate (TEOS), continue to stir for 2...

Embodiment 2

[0045] The CpG nucleic acid drug delivery system provided in this example comprises a carrier and a CpG nucleic acid drug stored in the carrier, the carrier is an amino-modified mesoporous silica nanoparticle, and the CpG nucleic acid drug is a CpG oligodeoxynucleus containing 72 base pairs nucleotides, namely:

[0046] 5'-TCAGAGAGTTAGAGAGTTAGAGAGTCAGAGAGTTAGAGAGTTAGAGAGTCAGAGGTTAGAGAGTTAGAGAG-3'.

[0047] The aminosilane coupling agent used in the preparation method of the CpG nucleic acid drug delivery system is γ-aminopropyltriethoxysilane, the silicon source used is ethyl orthosilicate, and the surfactant used is cetyl p- Tosylate, the cosolvent that adopts is triethanolamine, specifically comprises following two steps:

[0048] Step 1: Dissolve 3eq of cetyl p-toluenesulfonate (CTAT) and 5eq of triethanolamine (TEA) in 4000eq of deionized water at 80°C, stir for 1 hour to dissolve completely; then slowly add After 16eq of tetraethyl orthosilicate (TEOS) and 2eq of γ-amin...

Embodiment 3

[0053] The CpG nucleic acid drug used in this example is the CpG oligodeoxynucleotide used in Example 1, and the carrier used is the carrier prepared in Example 1.

[0054] The carrier prepared in Example 1 was dispersed in deionized water to prepare a 1 μg / μl suspension. The suspension and the CpG nucleic acid drug were mixed at a mass ratio of 5:1 to prepare a suspension of the two, then shaken in a shaker at room temperature for 4 hours, centrifuged, and washed with deionized water to obtain a CpG nucleic acid drug storage The amino-modified mesoporous silica nanoparticles are the target CpG nucleic acid drug delivery system.

[0055] The obtained CpG nucleic acid drug delivery system was measured by an ultramicro spectrophotometer, wherein the storage capacity of the CpG nucleic acid drug was 116 μg / mg.

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Abstract

The invention provides a CpG nucleic acid drug conveying system. The CpG nucleic acid drug conveying system is characterized in that the CpG nucleic acid drug conveying system comprises a vector and a CpG nucleic acid drug stored in the vector, 50-155[mu]g of the CpG nucleic acid drug is stored in 1mg of the vector, the vector is an amino silane coupling agent modied meso-porous silicon oxide nanoparticle, the particle size of the particle is 50-100nm, the meso-pore aperture is 2-15nm, and the CpG nucleic acid drug is CpG oligodeoxynucleotide, and contains 12-72 base pairs. The invention also provides a making method of the CpG nucleic acid drug conveying system. The CpG nucleic acid drug conveying system has a large CpG nucleic acid drug storage ability, and can be efficiently endocytosed into endosome by cells in order to substantially improve the secretion level of interleukin IL-6 and IgG antibody, so the pollen allergy inhibition and treatment effects are improved.

Description

technical field [0001] The invention relates to a CpG nucleic acid drug delivery system and a preparation method thereof, belonging to the field of pharmaceutical preparations. Background technique [0002] Pollen allergy is a common allergic symptom in people's life. In severe cases, it can also induce bronchitis, bronchial asthma and pulmonary heart disease. If it is not treated in time, it may be life-threatening. At present, the prevalence of pollen allergy in the world has reached about 5% to 10%, and the number of patients in our country is also increasing year by year. The pathogenesis is that the mast cells on the nasal mucosa of people with allergic constitution contain immunoglobulin IgE (Immunoglobulin E). The invading pollen binds to the IgE antibody, degranulates the mast cells, and releases the allergic mediator histamine, which makes the capillary Increased vascular permeability can cause allergic reactions such as mucosal edema, increased glandular secretion...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K31/711A61K47/04A61P37/08
Inventor 朱钰方陶翠莲
Owner UNIV OF SHANGHAI FOR SCI & TECH
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