Daunorubicin-containing medicine, preparation method of daunorubicin-containing medicine, medical composition and application of daunorubicin-containing medicine

A daunorubicin and drug technology, applied in the field of medicine, can solve the problems of difficult connection, non-toxic degradation, impact, toxicity and self-design contradiction of transfection activity

Active Publication Date: 2020-04-07
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.
[0006] Therefore, how to improve the delivery reliability of the existing small molecule drug daunorubicin is one of the difficulties in solving the current limited clinical application of daunorubicin.

Method used

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  • Daunorubicin-containing medicine, preparation method of daunorubicin-containing medicine, medical composition and application of daunorubicin-containing medicine
  • Daunorubicin-containing medicine, preparation method of daunorubicin-containing medicine, medical composition and application of daunorubicin-containing medicine
  • Daunorubicin-containing medicine, preparation method of daunorubicin-containing medicine, medical composition and application of daunorubicin-containing medicine

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Experimental program
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preparation example Construction

[0156] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned daunorubicin-containing drug, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; by means of physical connection and / or covalent connection The daunorubicin is mounted on the nucleic acid nanoparticles to obtain the daunorubicin-containing drug.

[0157] When physically linked, daunorubicin is usually intercalated between GC base pairs by physical intercalation. In the case of covalent linkage, daunorubicin usually undergoes a chemical reaction with the amino group outside the G ring to form a covalent linkage. The daunorubicin-containing drug prepared by the above-mentioned method can have better targeting after the target head is modified, can stably deliver the daunorubicin, and has high reliability.

[0158] In a preferred embodiment, the step of mounting daunorubicin by physical connectio...

Embodiment 1

[0180] 1. RNA and DNA nanoparticle carriers:

[0181] (1) The base sequences of the three polynucleotides that make up the RNA nanoparticles are shown in Table 1:

[0182] Table 1:

[0183]

[0184] (2) Three polynucleotide base sequences of DNA nanoparticles

[0185] 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.

[0186] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0187] 2. Self-assembly experimental steps:

[0188] (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;

[0189] (2) Heat the mixed solution to 80°C / 95°C (the RNA assembly temperature is 80°C, and the DNA assembly temperature is 95°...

Embodiment 2

[0200] 1. Seven groups of short-sequence RNA nanoparticle carriers:

[0201] (1) The base sequences of the three polynucleotides of the seven groups of RNA nanoparticles are shown in Table 2 to Table 8:

[0202] Table 2: R-1

[0203]

[0204] Table 3: R-2

[0205]

[0206] Table 4: R-3

[0207]

[0208] Table 5: R-4

[0209]

[0210] Table 6: R-5

[0211]

[0212] Table 7: R-6

[0213]

[0214] Table 8: R-7

[0215]

[0216] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0217] 2. Self-assembly experimental steps:

[0218] (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;

[0219] (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;

[0220] (3) Load the product onto an 8% (m / v) non-denaturing P...

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Abstract

The application of the invention provides a daunorubicin-containing medicine, a preparation method of the daunorubicin-containing medicine, a medical composition and an application of the daunorubicin-containing medicine. The medicine comprises nucleic acid nanometer particles and daunorubicin, wherein the daunorubicin is mounted on the nucleic acid nanometer particles, the nucleic acid nanometerparticles comprise nucleic acid structural domains, the nucleic acid structural domains include an a sequence, a b sequence and a c sequence, the a sequence includes an a1 sequence or a sequence obtained in a manner that one or more basic groups of the a1 sequence are inserted, deleted or replaced, the b sequence includes a b1 sequence or a sequence obtained in a manner that one or more basic groups of the b1 sequence are inserted, deleted or replaced, and the c sequence includes a c1 sequence or a sequence obtained in a manner that one or more basic groups of the c1 sequence are inserted, deleted or replaced. According to the daunorubicin-containing medicine provided by the application of the invention, after the nucleic acid structural domains are subjected to target head modification, the daunorubicin-containing medicine has better target properties, can steadily deliver the daunorubicin, and is high in reliability.

Description

technical field [0001] The application relates to the field of medicine, in particular, to a drug containing daunorubicin, its preparation method, pharmaceutical composition and application. Background technique [0002] Daunorubicin (Daunorubicin, CSA: 20830-81-3, molecular formula: C 27 h 29 NO 10 , molecular weight: 527.52) is mainly used for acute lymphocytic or myeloid leukemia resistant to commonly used antineoplastic drugs, but the remission period is short, so it needs to be combined with other drugs. It is orange-red needle crystal, easily soluble in water. Its aqueous solution is quite stable, and its effect is the same as that of doxorubicin. It can inhibit the synthesis of RNA and DNA by intercalating DNA, especially for RNA, and acts selectively on purine nucleosides. [0003] Currently, antitumor antibiotics, including daunorubicin, must be administered in large doses of chemotherapeutic drugs in order to achieve effective therapeutic levels at the tumor si...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/54A61K47/55A61K9/51A61K47/26A61K31/704A61P35/02A61P35/00
CPCA61K47/6929A61K47/549A61K47/55A61K9/5123A61K31/704A61P35/02A61P35/00
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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