Small interfering ribonucleic acid-containing pharmaceutical composition and application thereof

A technology of small interfering nucleic acid and composition, applied in the field of biomedicine, can solve the problems of reduction, weak reduction of surface antigen, reduction of HBV DNA level, etc., and achieves good therapeutic effect, excellent inhibition efficiency, and reduction of surface antigen expression.

Active Publication Date: 2018-06-29
SUZHOU RIBO LIFE SCIENCE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the other hand, for hepatitis B, traditional drugs only have a reducing effect on HBV DNA, and the reducing effect on surface antigen is extremely weak, while siRNA drugs can block HBV from the mRNA level based on the mechanism of RNA interference (RNA interference, RNAi). cut off, thereby reducing the levels of HBV DNA and HBsAg at the same time
However, since siRNA works in a sequence-specific manner, it is rare for a single siRNA drug to cover multiple genotypes

Method used

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  • Small interfering ribonucleic acid-containing pharmaceutical composition and application thereof
  • Small interfering ribonucleic acid-containing pharmaceutical composition and application thereof
  • Small interfering ribonucleic acid-containing pharmaceutical composition and application thereof

Examples

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Embodiment

[0100] The present invention is further described in detail by the following examples, but the present invention is not limited to these examples. It should be noted that, in the following examples, although only modified siRNA X2M2 and siRNA X30M are used to illustrate the present invention, the pharmaceutical composition containing unmodified siRNA X2M2 and siRNA X30M also has activity and certain stability sex.

[0101] Unless otherwise specified, the reagents and media used in the following examples are all commercially available, and the nucleic acid electrophoresis, real-time PCR and other operations used are all performed according to conventional protocols. For example, it can be carried out as described in Molecular Cloning (Cold Spring Harbor Laboratory Press (1989)).

preparation Embodiment 1

[0103] The siRNAs listed in Table 1 were obtained by conventional solid-phase synthesis methods. An equimolar mixture of sense and antisense strands is dissolved with annealing salt solution, followed by routine annealing to form siRNA duplexes. Among them, NC is an irrelevant sequence that has no targeting effect on HBV mRNA. As a negative control, it will also be referred to as control siRNA hereinafter; the remaining siRNAs (siRNA X2M2 and siRNAX30M) are siRNAs that specifically target HBV, and they will also be referred to as siRNA hereinafter. Called the test siRNA.

[0104] Table 1 Sequence of siRNA

[0105]

[0106] Note: Capital letters C, G, U, A and T indicate the base composition of nucleotides; lowercase letter d indicates that the nucleotide on the right side of the letter d is deoxyribonucleotide; lowercase letter m indicates the letter m The ribose group of a nucleotide on the left is a 2'-methoxyribose group in which the 2'-hydroxyl is replaced by a methox...

preparation Embodiment 2

[0108] Three dry powder lipid compounds (i.e., amine-containing compound, helper lipid, pegylated lipid) were suspended and mixed in ethanol at a molar ratio of 59:29:12, the total mass concentration of the three lipid compounds About 8.85mg / ml. The synthesized siRNA listed in Table 1 is dissolved in 200mM sodium acetate (pH 5.2) solution, so that the concentration of siRNA is 0.2mg / ml (for the situation of using siRNA X2M2 and siRNA X30M alone, the concentration of siRNA is 0.2mg / ml; for the combined application of siRNAX2M2 and siRNAX30M, the two siRNAs were mixed in equal proportions, that is, the concentration of each siRNA was 0.1 mg / ml). The resulting lipid ethanol solution and siRNA sodium acetate aqueous solution were mixed very rapidly at a volume ratio of 1:3. The specific composition of the liposome formulation obtained after mixing is described in Table 2.

[0109] The composition of table 2 liposome preparation

[0110]

[0111] The resulting liposome formu...

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Abstract

The invention provides a small interfering ribonucleic acid-containing pharmaceutical composition and application thereof in preparation of medicines for preventing and / or treating hepatitis B. The small interfering ribonucleic acid-containing pharmaceutical composition contains two small interfering ribonucleic acids specified at different genotypes of the hepatitis B virus and serving as activeingredients, can achieve an effect of extensively covering multiple genotypes of HBV, has a synergistic effect in the aspect of inhibiting the multiple genotypes of the HBV, can simultaneously lower the level of HBsAg, and has the clinical application potential.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a small interfering nucleic acid pharmaceutical composition and its application. Background technique [0002] Viral hepatitis B (also known as hepatitis B or hepatitis B) is a class of infectious diseases that seriously threaten the world, especially China. According to the genotype, HBV can be divided into 8 types: A, B, C, D, E, F, G, and H. These genotypes have at least 8% difference in sequence and have different geographical distribution characteristics. Among them, type A is distributed all over the world; types B and C are mainly distributed in Asia; type D is mainly distributed in America, southern Europe, and Australia and the Middle East; type E is mainly distributed in Africa; type F is distributed in Native Americans and Polynesia; type G is distributed in the Americas; type H is found in the United States. [0003] At present, interferon and nucleoside analogu...

Claims

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Application Information

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IPC IPC(8): A61K31/713A61P31/20
CPCA61K31/713A61K2300/00
Inventor 张鸿雁高山
Owner SUZHOU RIBO LIFE SCIENCE CO LTD
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