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Medicine containing 10-hydroxycamptothecin, its preparation method, pharmaceutical composition and application thereof

A technology of hydroxycamptothecin and drugs, applied in the field of medicine, can solve problems such as impact, toxicity and transfection activity, self-design contradictions, difficulty in ensuring targeting groups, etc.

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, but 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, it is difficult to achieve non-toxic degradation of its connection in vivo

Method used

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  • Medicine containing 10-hydroxycamptothecin, its preparation method, pharmaceutical composition and application thereof
  • Medicine containing 10-hydroxycamptothecin, its preparation method, pharmaceutical composition and application thereof
  • Medicine containing 10-hydroxycamptothecin, its preparation method, pharmaceutical composition and application thereof

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preparation example Construction

[0153] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned 10-hydroxycamptothecin-containing drug, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; through physical connection and / or covalent connection 10-Hydroxycamptothecin is mounted on nucleic acid nanoparticles in a manner to obtain a drug containing 10-Hydroxycamptothecin.

[0154] When physically linked, 10-hydroxycamptothecin usually intercalates between GC base pairs by physical intercalation. When the connection is carried out by covalent connection, 10-hydroxycamptothecin usually reacts with the amino group outside the G ring to form a covalent connection. The drug containing 10-hydroxycamptothecin prepared by the above method can have better targeting after the target head is modified, and can stably deliver 10-hydroxycamptothecin with high reliability.

[0155] In a preferred embodiment...

Embodiment 1

[0177] 1. RNA and DNA nanoparticle carriers:

[0178] (1) The three polynucleotide base sequences that make up the RNA nanoparticles, see Table 1 for details:

[0179] Table 1:

[0180]

[0181] (2) Three polynucleotide base sequences of DNA nanoparticles.

[0182] 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.

[0183] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0184] 2. Self-assembly experimental steps:

[0185] (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;

[0186] (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

[0197] 1. Seven groups of short-sequence RNA nanoparticle carriers:

[0198] (1) Seven groups of three polynucleotide base sequences that make up RNA nanoparticles:

[0199] Table 2: R-1:

[0200]

[0201] Table 3: R-2:

[0202]

[0203] Table 4: R-3:

[0204]

[0205] Table 5: R-4:

[0206]

[0207] Table 6: R-5:

[0208]

[0209] Table 7: R-6:

[0210]

[0211] Table 8: R-7:

[0212]

[0213] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0214] 2. Self-assembly experimental steps:

[0215] (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;

[0216] (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;

[0217] (3) Load the product onto an 8% (m / v) non-denaturing PAGE gel and purify the comple...

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Abstract

The application provides a medicine containing 10-hydroxycamptothecin, its preparation method, pharmaceutical composition and application. The drug includes nucleic acid nanoparticles and 10-hydroxycamptothecin, and 10-hydroxycamptothecin is mounted on the nucleic acid nanoparticles; the nucleic acid nanoparticles include a nucleic acid domain, and the nucleic acid domain includes a sequence, b sequence and c sequence, The a sequence includes the a1 sequence or the sequence in which at least one base insertion, deletion or substitution occurs in the a1 sequence, the b sequence includes the b1 sequence or the sequence in which at least one base insertion, deletion or substitution occurs in the b1 sequence, and the c sequence includes the c1 sequence or the c1 sequence A sequence in which at least one base has been inserted, deleted or substituted. The drug containing 10-hydroxycamptothecin provided by the present application, after the nucleic acid domain is modified by the target head, can have better targeting, can stably deliver 10-hydroxycamptothecin, and has high reliability.

Description

technical field [0001] The application relates to the field of medicine, in particular, to a medicine containing 10-hydroxycamptothecin, its preparation method, pharmaceutical composition and application. Background technique [0002] At present, cancer has become one of the major diseases that threaten human health and quality of life. Finding effective drugs and treatment strategies for cancer treatment has become an urgent problem to be solved in the entire medical field around the world. 10-Hydroxycamptothecin is a commonly used drug in the treatment of liver cancer, gastric cancer, head and neck cancer or leukemia, and plays an important role in medical oncology. [0003] In order to alleviate the side effects caused by the poor targeting of drug active ingredients, drug delivery carriers have emerged. Their main function is to carry drug active ingredients and transport the active ingredients into blood or tissue cells to treat diseases. At present, there are various ...

Claims

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Application Information

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IPC IPC(8): A61K47/54A61K47/55A61K47/69A61K9/51A61K47/26A61K31/4745A61P35/00A61P35/02
CPCA61K47/549A61K47/55A61K47/6929A61K9/5123A61K31/4745A61P35/00A61P35/02
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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