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Drug containing daunorubicin, preparation method thereof, pharmaceutical composition and application thereof

A daunorubicin and drug technology, applied in the field of medicine, can solve the problem of the small molecule drug daunorubicin delivery reliability. Problems such as poisoning and degradation, to achieve high reliability, improve stability, and reduce the chance of contact

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.
[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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  • Drug containing daunorubicin, preparation method thereof, pharmaceutical composition and application thereof
  • Drug containing daunorubicin, preparation method thereof, pharmaceutical composition and application thereof
  • Drug containing daunorubicin, preparation method thereof, pharmaceutical composition and application thereof

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preparation example Construction

[0156] According to the second aspect of the present application, there is also provided a preparation method of the above-mentioned daunorubicin-containing medicine, which comprises the following steps: providing any 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 a drug containing daunorubicin.

[0157] When physically linked, daunorubicin is usually physically intercalated between the GC base pairs. When the connection is made by covalent connection, daunorubicin usually chemically reacts with the amino group outside the G ring to form a covalent connection. The daunorubicin-containing medicament prepared by the above-mentioned method can have better targeting ability after being modified by the target head, can deliver daunorubicin stably, and has high reliability.

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

Embodiment 1

[0180] 1. RNA and DNA nanoparticle carriers:

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

[0182] Table 1:

[0183]

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

[0185] 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.

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

[0187] Second, the self-assembly experimental steps:

[0188] (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;

[0189] (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), and a...

Embodiment 2

[0200] 1. 7 groups of short-sequence RNA nanoparticle carriers:

[0201] (1) The base sequences of the three polynucleotides that make up the 7 groups of RNA nanoparticles are shown in Tables 2 to 8 respectively:

[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] Second, the self-assembly experimental steps:

[0218] (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;

[0219] (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;

[0220] (3) Load the product onto...

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Abstract

The application provides a daunorubicin-containing medicine, its preparation method, pharmaceutical composition and application. The drug includes nucleic acid nanoparticles and daunorubicin, and the daunorubicin 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 The sequence or a1 sequence has at least one base insertion, deletion or substitution sequence, the b sequence contains the b1 sequence or the b1 sequence has at least one base insertion, deletion or substitution, and the c sequence contains the c1 sequence or the c1 sequence has at least one base substitution. Sequences of insertions, deletions or substitutions. The daunorubicin-containing drug provided by the present application, after the nucleic acid domain is modified by the target head, can have better targeting, can deliver daunorubicin stably, and has high reliability.

Description

technical field [0001] The present application relates to the field of medicine, in particular, to a daunorubicin-containing medicine, 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 lymphoblastic 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, and has a particularly obvious effect on RNA, selectively acting on purine nucleosides. [0003] Currently, antitumor antibiotics, including daunorubicin, must be administered in large doses of chemotherapeutic drugs in order to achieve effect...

Claims

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Application Information

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Patent Type & Authority Patents(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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