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Drug containing doxorubicin and preparation method thereof

A doxorubicin and drug technology, applied in the field of doxorubicin-containing drugs and their preparation, can solve the problem of difficult connection, non-toxic degradation, self-design contradiction between toxicity and transfection activity, and non-nucleic acid drug delivery effects are of no value reports, etc.

Active Publication Date: 2022-07-22
BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cationic liposomes have high transfection activity in vivo and in vitro, however, because the positive charge on the surface affects their normal distribution in vivo, at the same time, cationic lipids can cause immunogenicity and inflammatory responses in animal experiments
The development of polycationic gene carriers has been relatively mature. However, it is difficult to ensure that the targeting group is on the surface of the structure in the structural design, and there is a self-design contradiction between toxicity and transfection activity. At the same time, its connection is difficult to achieve non-toxic degradation in vivo.
However, it can be seen from the above that the existing research on non-viral vectors focuses more on nucleic acid drugs, and there is no valuable report on the delivery effect of non-nucleic acid drugs.
[0008] Therefore, how to improve the delivery reliability of doxorubicin is the key to solve the current limited clinical application of doxorubicin.

Method used

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  • Drug containing doxorubicin and preparation method thereof
  • Drug containing doxorubicin and preparation method thereof
  • Drug containing doxorubicin and preparation method thereof

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preparation example Construction

[0147] According to another aspect of the present invention, there is also provided a method for preparing the above-mentioned drug containing doxorubicin, which comprises the following steps: providing the above-mentioned nucleic acid nanoparticles; Mounted on nucleic acid nanoparticles to obtain a drug containing doxorubicin.

[0148] When physically linked, doxorubicin is usually physically intercalated between the GC base pairs. When the covalent connection is used for connection, doxorubicin usually chemically reacts with the amino group outside the G ring to form a covalent connection. The drug containing doxorubicin prepared by the above method has good targeting ability after modification of the target head, can deliver doxorubicin stably, and has high reliability.

[0149] In a preferred embodiment, the step of mounting doxorubicin by physical connection includes: mixing and stirring doxorubicin, nucleic acid nanoparticles and the first solvent to obtain a premixed s...

Embodiment 1

[0169] 1. RNA and DNA nanoparticle carriers:

[0170] (1) The three polynucleotide base sequences that make up the RNA nanoparticle are specifically shown in Table 1:

[0171] Table 1:

[0172]

[0173] (2) Three polynucleotide base sequences of DNA nanoparticles.

[0174] The DNA adopts the same sequence as the RNA described above, except that T replaces U. Among them, the molecular weight of the a chain is 8802.66, the molecular weight of the b chain is 8280.33, and the molecular weight of the c chain is 9605.2.

[0175] The a, b and c chains of the above RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0176] Second, the self-assembly experimental steps:

[0177] (1) Dissolve RNA or DNA single strands a, b, and c in DEPC water or TMS buffer at a molar ratio of 1:1:1;

[0178] (2) Heating the mixed solution to 80°C / 95°C (wherein the RNA assembly temperature is 80°C and the DNA assembly temperature is 95°C), ...

Embodiment 2

[0189] 1. 7 groups of short-sequence RNA nanoparticle carriers:

[0190] (1) 7 groups of three polynucleotide base sequences that make up RNA nanoparticles:

[0191] Table 2: R-1:

[0192]

[0193]

[0194] Table 3: R-2:

[0195]

[0196] Table 4: R-3:

[0197]

[0198] Table 5: R-4:

[0199]

[0200]

[0201] Table 6: R-5:

[0202]

[0203] Table 7: R-6:

[0204]

[0205] Table 8: R-7:

[0206]

[0207]

[0208] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0209] Second, the self-assembly experimental steps:

[0210] (1) Mix and dissolve RNA single strands a, b, and c simultaneously in DEPC water or TMS buffer at a molar ratio of 1:1:1;

[0211] (2) heating the mixed solution to 80°C, keeping the temperature for 5min and then slowly cooling to room temperature at a rate of 2°C / min;

[0212] (3) Load the product onto an 8% (m / v) ...

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Abstract

The invention provides a drug containing doxorubicin and a preparation method. The drug includes nucleic acid nanoparticles and doxorubicin, and the doxorubicin is mounted on the nucleic acid nanoparticles; the nucleic acid nanoparticles include a nucleic acid domain, the nucleic acid domain includes a sequence, b sequence and c sequence, and the a sequence includes a1 sequence or A1 sequence contains at least one base insertion, deletion or substitution sequence, b sequence contains b1 sequence or b1 sequence contains at least one base insertion, deletion or substitution sequence, c sequence contains c1 sequence or c1 sequence contains at least one base insertion , deleted or substituted sequences. The drug containing doxorubicin provided by the present invention has good targeting ability after the nucleic acid domain is modified by the target head, can deliver doxorubicin stably, and has high reliability.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a medicine containing doxorubicin and a preparation method thereof. Background technique [0002] Liver cancer is one of the most common malignant tumors. It refers to malignant tumors that occur in the liver, including primary liver cancer and metastatic liver cancer. People often say liver cancer refers to primary liver cancer. Primary liver cancer is one of the most common malignant tumors in the clinic. Currently, the incidence in my country accounts for more than half of the world's patients, accounting for 55% of the world's liver cancer patients. [0003] Doxorubicin is an anti-tumor antibiotic, which is easy to penetrate the cell membrane and enter the cell, and then quickly combines with the nucleus, inserts into the DNA molecule, forms a stable complex, inhibits the synthesis of DNA, RNA and protein, and is effective for tumors of various growth cycles. Cells are killed. Since...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K47/55A61K47/26A61K31/704A61K45/06A61P35/00
CPCA61K47/549A61K47/55A61K47/26A61K31/704A61K45/06A61P35/00A61K2300/00
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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