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Medicine containing mitoxantrone, preparation method thereof, pharmaceutical composition and application thereof

A technology of mitoxantrone and drugs, applied in the field of mitoxantrone-containing drugs, can solve the limited clinical application of small-molecule drug mitoxantrone delivery reliability, the contradiction between toxicity and transfection activity, and the difficulty of connection Non-toxic degradation and other issues, to achieve high reliability, improve stability, and reduce the chance of contact

Active Publication Date: 2022-07-26
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 mitoxantrone is one of the difficulties in solving the current limited clinical application of mitoxantrone.

Method used

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  • Medicine containing mitoxantrone, preparation method thereof, pharmaceutical composition and application thereof
  • Medicine containing mitoxantrone, preparation method thereof, pharmaceutical composition and application thereof
  • Medicine containing mitoxantrone, preparation method thereof, pharmaceutical composition and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0157] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned mitoxantrone-containing medicine, comprising the following steps: providing any of the above-mentioned nucleic acid nanoparticles; by means of physical connection and / or covalent connection The mitoxantrone is mounted on the nucleic acid nanoparticles to obtain the mitoxantrone-containing medicine.

[0158] When physically linked, mitoxantrone is usually physically intercalated between GC base pairs. When the connection is made by covalent connection, mitoxantrone usually chemically reacts with the amino group outside the G ring to form a covalent connection. The mitoxantrone-containing medicine prepared by the above-mentioned method can have good targeting ability after modification of the target head, and can deliver mitoxantrone stably with high reliability.

[0159] In a preferred embodiment, the step of mounting mitoxantrone by physical conn...

Embodiment 1

[0182] 1. RNA and DNA nanoparticle carriers:

[0183] (1) The three polynucleotide base sequences that make up the RNA nanoparticle are specifically shown in Table 1:

[0184] Table 1:

[0185]

[0186] (2) Three polynucleotide base sequences of DNA nanoparticles.

[0187] 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.

[0188] The a, b and c chains of the above RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0189] Second, the self-assembly experimental steps:

[0190] (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;

[0191] (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

[0202] 1. 7 groups of short-sequence RNA nanoparticle carriers:

[0203] (1) 7 groups of three polynucleotide base sequences that make up RNA nanoparticles:

[0204] Table 2: R-1:

[0205]

[0206]

[0207] Table 3: R-2:

[0208]

[0209] Table 4: R-3:

[0210]

[0211] Table 5: R-4:

[0212]

[0213]

[0214] Table 6: R-5:

[0215]

[0216] Table 7: R-6:

[0217]

[0218] Table 8: R-7:

[0219]

[0220]

[0221] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0222] Second, the self-assembly experimental steps:

[0223] (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;

[0224] (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;

[0225] (3) Load the product onto an 8% (m / v...

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Abstract

The application provides a medicine containing mitoxantrone, its preparation method, pharmaceutical composition and application. The drug includes nucleic acid nanoparticles and mitoxantrone, and the mitoxantrone 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 mitoxantrone-containing medicine provided by the present application, after the nucleic acid domain is modified by the target head, can have better targeting, can deliver mitoxantrone stably, and has high reliability.

Description

technical field [0001] The present application relates to the field of medicine, in particular, to a medicine containing mitoxantrone, its preparation method, pharmaceutical composition and application. Background technique [0002] Mitoxantrone (Mitoxantrone, CSA: 65271-80-9, molecular formula: C 22 H 28 N 4 O 6 , molecular weight: 444.481) is an anti-tumor antibiotic, the mechanism of action is similar to that of doxorubicin, because it has no amino sugar structure, does not produce free radicals, and has the effect of inhibiting lipid peroxidation, so it is less toxic to the heart. It is mainly used for the treatment of breast cancer, malignant lymphoma, gastric cancer, intestinal cancer, leukemia, bladder cancer, liver cancer, multiple myeloma, malignant mesothelioma and ovarian cancer. [0003] Currently, antitumor antibiotics, including mitoxantrone, must be administered in large doses of chemotherapeutic drugs in order to achieve effective therapeutic levels at th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K47/69A61K9/51A61K47/26A61K31/136A61P35/00A61P35/02
CPCA61K47/549A61K47/6929A61K9/5123A61K31/136A61P35/00A61P35/02
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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