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Adriamycin-containing medicine and preparation method thereof

A doxorubicin and drug technology, applied in the field of doxorubicin-containing drugs and their preparation, can solve the contradiction between toxicity and transfection activity, the non-nucleic acid drug delivery effect has no valuable reports, and the connection is difficult. Toxic degradation and other issues

Active Publication Date: 2020-01-21
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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  • Adriamycin-containing medicine and preparation method thereof
  • Adriamycin-containing medicine and preparation method thereof
  • Adriamycin-containing medicine 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 includes the following steps: providing the above-mentioned nucleic acid nanoparticles; Mounted on the nucleic acid nanoparticles to obtain a drug containing doxorubicin.

[0148] When using physical linkage, doxorubicin usually intercalates between GC base pairs by physical intercalation. In the case of covalent linkage, doxorubicin usually reacts with the amino group outside the G ring to form a covalent linkage. The doxorubicin-containing drug prepared by the above method can have better targeting after the target head is modified, can stably deliver the doxorubicin, and has high reliability.

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

Embodiment 1

[0169] 1. RNA and DNA nanoparticle carriers:

[0170] (1) The three polynucleotide base sequences that make up the RNA nanoparticles, see Table 1 for details:

[0171] Table 1:

[0172]

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

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

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

[0176] 2. Self-assembly experimental steps:

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

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

Embodiment 2

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

[0190] (1) Seven 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] 2. Self-assembly experimental steps:

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

[0211] (2) Heat the mixed solution to 80°C, keep it for 5min and then cool down slowly to room temperature at a rate of 2°C / min;

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

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Abstract

The invention provides adriamycin-containing medicine and a preparation method thereof. The medicine includes a nucleic acid nanoparticle and adriamycin, and the adriamycin is mounted on the nucleic acid nanoparticle; and the nucleic acid nanoparticle includes a nucleic acid structural domain, the nucleic acid structural domain contains an a sequence, a b sequence and a c sequence, and the a sequence contains an a1 sequence or a sequence of the a1 sequence in which at least one base is inserted, missed or replaced, the b sequence contains a b1 sequence or a sequence of the b sequence in whichat least one base is inserted, missed or replaced, and the c sequence contains a c1 sequence or a sequence of the c sequence in which at least one base is inserted, missed or replaced. According to the adriamycin-containing medicine, after the nucleic acid structural domain is modified by a target, targetability is good, adriamycin can be stably delivered, and reliability is high.

Description

technical field [0001] The invention relates to the field of medicines, 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 usually refer to primary liver cancer when they say liver cancer. Primary liver cancer is one of the most common clinical malignant tumors. At present, the number of cases in my country accounts for more than half of the world, accounting for 55% of the global liver cancer patients. [0003] Doxorubicin is an anti-tumor antibiotic that easily penetrates the cell membrane and enters the cell, then quickly binds to 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 the 1970s, ...

Claims

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Application Information

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Patent Type & Authority Applications(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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