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A nucleic acid transmembrane transport carrier and its preparation method

A technology for transmembrane transport and nucleic acid, which is applied in the direction of pharmaceutical formulations, emulsion delivery, and medical preparations of non-active ingredients, etc. It can solve problems such as limited ability to enter cells, nuclease hydrolysis, and reduced activity of therapeutic nucleic acids. Achieve good biocompatibility and high environmental friendliness

Active Publication Date: 2022-02-11
JIANGSU RENMING BIOLOGICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current clinical application of therapeutic nucleic acids still faces two problems: first, it is easily hydrolyzed by nucleases in plasma; second, the ability to enter cells is limited
However, these chemical modifications reduce the activity of the therapeutic nucleic acid while protecting it from nuclease hydrolysis

Method used

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  • A nucleic acid transmembrane transport carrier and its preparation method
  • A nucleic acid transmembrane transport carrier and its preparation method
  • A nucleic acid transmembrane transport carrier and its preparation method

Examples

Experimental program
Comparison scheme
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preparation example Construction

[0030] The preparation method of the present invention will be further described in detail in conjunction with specific examples below. It should be understood that the following examples are only for illustrating and explaining the present invention, and should not be construed as limiting the protection scope of the present invention. All technologies realized based on the above contents of the present invention are covered within the scope of protection intended by the present invention.

[0031] The experimental methods used in the following examples are conventional methods unless otherwise specified; the reagents and materials used in the following examples can be obtained from commercial sources unless otherwise specified.

[0032] Refer below figure 1 Embodiments of the present invention are explained in detail.

[0033] figure 1 The process of interfacial acylation reaction of chitosan was shown. Chitosan chains first exist in the aqueous solution in the form of c...

Embodiment 1

[0035] 1) Preparation of fatty acid modified chitosan

[0036] Accurately weigh a certain amount of chitosan, dissolve it in 10mL of 1% acetic acid solution, transfer it to a three-necked flask, place it in a low-temperature refrigerator, and slowly add a certain amount of triethyl ether solution dropwise at 25°C under the condition of low-speed stirring. The dichloromethane solution of the amine and the dichloromethane solution dissolved in stearic acid and thionyl chloride were all added dropwise, and the reaction was stirred for 3 hours. The post-treatment conditions are as follows: first separate the water phase, wash the water phase twice with 100ml of dichloromethane, combine the organic phase, evaporate to dryness by rotary evaporation, wash with 100ml of water several times, filter and freeze-dry to constant weight to obtain light yellow fatty acid Modified chitosan.

[0037] 2) Preparation of nucleic acid transmembrane transport vector

[0038] Dissolve the fatty ac...

Embodiment 1-8 and comparative example 1-4

[0044] The processing steps of Examples 1-8 and Comparative Examples 1-4 are carried out with reference to the above reaction process, and the difference is only in the molecular weight of chitosan, the type of fatty acid, the material ratio of the transmembrane transport carrier and the difference in the nucleic acid type of different loads, specifically As shown in Table 1:

[0045] Table 1

[0046]

[0047]

[0048] The encapsulation efficiency of each nucleic acid transmembrane transport carrier is shown in Table 2.

[0049] Table 2

[0050] Chitosan (molecular weight) cholesterol nucleic acid The molar ratio of Encapsulation rate (%) Example 1 10000-50000 cholesterol 16C_GFP 22-mer 10.0:0.2:1.0 94.3 Example 2 50000-100000 cholesterol 16C_GFP 22-mer 5.0:0.2:1.0 93.5 Example 3 10000-50000 cholesterol Tom eGFP 22-mer 10.0:0.2:1.0 96.2 Example 4 50000-100000 cholesterol Tom eGFP 22-mer 5.0:0.2:1.0 95.8...

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Abstract

The invention provides a nucleic acid transmembrane transport carrier and a preparation method thereof. The nucleic acid transmembrane transport carrier is composed of raw materials and loaded drugs, the raw materials include fatty acid modified chitosan and cholesterol, and the loaded drugs are nucleic acid substances. Since chitosan molecules contain a large number of amino groups, long-chain hydrophobic groups are introduced into chitosan structural units by interfacial reactions; thus the modified chitosan has both hydrophilic groups (amino sugar regions) and amphiphilic groups. Sexual group (sugar ester region); the pka of the amino sugar region amino group in fatty acid modified chitosan is below 6.5, which can provide a binding region with high affinity for nucleic acid substances; and the sugar in fatty acid modified chitosan The ester domains tend to form rod-like micelles or lamellar micelles, thereby physically protecting nucleic acids. The rod-shaped micelles or lamellar micelles are prone to flip when they approach the cell membrane, so that they are easy to insert into the cell membrane and provide power for the transmembrane transport of nucleic acid substances.

Description

technical field [0001] The present invention relates to the field of nucleic acid drug delivery bodies. Specifically, the present invention provides a preparation method of fatty acid-modified chitosan with "aminosugar region" and "sugar ester region", as well as the composition of the composition that is beneficial to the delivery of nucleic acid in vivo. In addition, the present invention provides methods for preparing such compositions and methods for determining the stability of such compositions in physiological environments, which can be used in the treatment of various diseases. Background technique [0002] Therapeutic nucleic acids include, for example, small interfering RNA (siRNA), microRNA (miRNA), antisense oligonucleotides, ribozymes, plasmids, and immunostimulatory nucleic acids. Such nucleic acids function through a variety of mechanisms. Therapeutic applications of RNAi are extremely broad, as siRNA and miRNA constructs can be synthesized against any nucle...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/113A61K47/36A61K47/28A61K31/7088
CPCA61K9/113A61K47/36A61K47/28A61K31/7088
Inventor 刘佳张立新那日松刘晓光赵熹冯献礼丁胜利
Owner JIANGSU RENMING BIOLOGICAL TECH CO LTD