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Medicine containing vincristine, its preparation method, pharmaceutical composition and application thereof

A vincristine and drug technology, applied in the field of medicine, can solve the limited clinical application of vincristine drug delivery reliability of small molecule drug vincristine, the self-design contradiction between toxicity and transfection activity, difficult connection and non-toxic degradation, etc. problems, to achieve the effect of high reliability, improved stability, and reduced opportunities for contact

Active Publication Date: 2022-05-20
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 vincristine is one of the difficulties in solving the current limited clinical application of vincristine drugs

Method used

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  • Medicine containing vincristine, its preparation method, pharmaceutical composition and application thereof
  • Medicine containing vincristine, its preparation method, pharmaceutical composition and application thereof
  • Medicine containing vincristine, its preparation method, pharmaceutical composition and application thereof

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preparation example Construction

[0154] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned vincristine-containing drug, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; The vincristine is loaded on the nucleic acid nanoparticles to obtain the vincristine-containing medicine.

[0155] When physically linked, vincristine is usually intercalated between GC base pairs by physical intercalation. When the covalent link is used for linking, vincristine usually reacts with the amino group outside the G ring to form a covalent link. The vincristine-containing drug prepared by the above method can have better targeting after the target head is modified, can deliver vincristine stably, and has high reliability.

[0156] In a preferred embodiment, the step of mounting vincristine through physical connection includes: mixing and stirring vincristine, nucleic acid nanoparticles and the first so...

Embodiment 1

[0179] 1. RNA and DNA nanoparticle carriers:

[0180] (1) The base sequences of the three polynucleotides that make up the RNA nanoparticles are shown in Table 1:

[0181] Table 1:

[0182]

[0183] (2) Three polynucleotide base sequences of DNA nanoparticles

[0184] 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.

[0185] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0186] 2. Self-assembly experimental steps:

[0187] (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;

[0188] (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

[0199] 1. Seven groups of short-sequence RNA nanoparticle carriers:

[0200] (1) The base sequences of the three polynucleotides of the seven groups of RNA nanoparticles are shown in Table 2 to Table 8:

[0201] Table 2: R-1

[0202]

[0203] Table 3: R-2

[0204]

[0205] Table 4: R-3

[0206]

[0207] Table 5: R-4

[0208]

[0209] Table 6: R-5

[0210]

[0211] Table 7: R-6

[0212]

[0213] Table 8: R-7

[0214]

[0215] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0216] 2. Self-assembly experimental steps:

[0217] (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;

[0218] (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;

[0219] (3) Load the product onto an 8% (m / v) non-denaturing...

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Abstract

The application provides a medicine containing vincristine, its preparation method, pharmaceutical composition and application. The drug includes nucleic acid nanoparticles and vincristine, and vincristine 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 an a1 sequence or The a1 sequence has at least one base insertion, deletion or substitution, 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 insertion , missing or substituted sequences. The drug containing vincristine provided by the present application, after the nucleic acid structure domain is modified by the target head, can have better targeting, can stably deliver vincristine, and has high reliability.

Description

technical field [0001] The application relates to the field of medicine, in particular, to a vincristine-containing medicine, its preparation method, pharmaceutical composition and application. Background technique [0002] Vincristine (Vincristine, Oncovin, VCR, molecular formula: C 46 h 56 N 4 o 10 , molecular weight 824.96, CAS No.: 57-22-7) is a bis-indole alkaloid, a natural plant antineoplastic drug. Mainly used for the treatment of acute lymphocytic leukemia, but also for the treatment of chronic lymphocytic leukemia, Hodgkin's lymphoma, lymphosarcoma, Ewing sarcoma, neuroblastoma, reticulocyte sarcoma, small cell carcinoma, gastrointestinal cancer, melanoma cancer and multiple myeloma and breast cancer. It has the effect of stopping cell division (mitosis) in metaphase. [0003] Currently, antitumor antibiotics, including vincristine, must be administered in large doses of chemotherapy drugs in order to achieve effective therapeutic levels at the tumor site, bu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K47/69A61K9/51A61K47/26A61K31/475A61P35/00A61P35/02
CPCA61K47/549A61K47/6929A61K9/5123A61K31/475A61P35/00A61P35/02
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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