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Gemcitabine-containing medicine and preparation method thereof, and pharmaceutical composition and application thereof

A technology of gemcitabine and drugs, which is applied in drug combinations, medical preparations containing active ingredients, drug delivery, etc., can solve the problem of the reliability of delivery of small molecule drug gemcitabine, the limited clinical application of gemcitabine drugs, the difficulty of connection, non-toxic degradation, impact, etc. question

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 gemcitabine is one of the difficulties in solving the current limited clinical application of gemcitabine.

Method used

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  • Gemcitabine-containing medicine and preparation method thereof, and pharmaceutical composition and application thereof
  • Gemcitabine-containing medicine and preparation method thereof, and pharmaceutical composition and application thereof
  • Gemcitabine-containing medicine and preparation method thereof, and 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 method for preparing the above-mentioned drug containing gemcitabine, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; Loaded on nucleic acid nanoparticles to obtain gemcitabine-containing drugs.

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

[0158] In a preferred embodiment, the step of mounting gemcitabine through physical connection includes: mixing and stirring gemcitabine, nucleic acid nanoparticles and the first solvent to obtain a premixed system; precipitating the ...

Embodiment 1

[0182] 1. RNA and DNA nanoparticle carriers:

[0183] (1) The base sequences of the three polynucleotides that make up the RNA nanoparticles are shown in Table 1:

[0184] Table 1:

[0185]

[0186]

[0187] (2) Three polynucleotide base sequences of DNA nanoparticles

[0188] 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.

[0189] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0190] 2. Self-assembly experimental steps:

[0191] (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;

[0192](2) Heat the mixed solution to 80°C / 95°C (the RNA assembly temperature is 80°C, and the DNA assembly tempera...

Embodiment 2

[0203] 1. Seven groups of short-sequence RNA nanoparticle carriers:

[0204] (1) The base sequences of the three polynucleotides of the seven groups of RNA nanoparticles are shown in Table 2 to Table 8:

[0205] Table 2: R-1

[0206]

[0207] Table 3: R-2

[0208]

[0209]

[0210] Table 4: R-3

[0211]

[0212] Table 5: R-4

[0213]

[0214] Table 6: R-5

[0215]

[0216]

[0217] Table 7: R-6

[0218]

[0219] Table 8: R-7

[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] 2. Self-assembly experimental steps:

[0223] (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;

[0224] (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;

[0225] (3) Load the product onto an...

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Abstract

The application provides a gemcitabine-containing medicine and a preparation method thereof, and a pharmaceutical composition and an application thereof. The medicine comprises nucleic acid nanoparticles and gemcitabine, and besides, the gemcitabine is carried on the nucleic acid nanoparticles; and the nucleic acid nanoparticles comprise a nucleic acid domain, the nucleic acid domain comprises a sequence a, a sequence b and a sequence c, the sequence a comprises a sequence a1 or a sequence of the sequence a1 with at least one base insertion, deletion or substitution, the sequence b comprises asequence b1 or a sequence of the sequence b1 with at least one base insertion, deletion or substitution, and the sequence c comprises a sequence c1 or a sequence of the sequence c1 with at least onebase insertion, deletion or substitution. After the nucleic acid structural domain is modified by a target head, the provided gemcitabine-containing medicine has relatively good targeting property, can stably deliver the gemcitabine and is very high in reliability.

Description

technical field [0001] The application relates to the field of medicine, in particular, to a medicine containing gemcitabine, its preparation method, pharmaceutical composition and application. Background technique [0002] Gemcitabine (Gemcitabine) is a new cytidine nucleoside derivative. Like cytarabine, it is activated by deoxycytosine kinase and metabolized by cytosine nucleoside deaminase after entering the human body. This product is a pyrimidine antineoplastic drug with the same mechanism of action as cytarabine. Its main metabolites are incorporated into DNA in cells and mainly act on the G1 / S phase. But the difference is that in addition to being incorporated into DNA, difluorodeoxycytidine can also inhibit nucleotide reductase, resulting in a decrease in deoxynucleoside triphosphate in cells; another difference from ara-C is that it can inhibit deoxycytidine Pyrimidine deaminase reduces the degradation of intracellular metabolites and has a self-enhancing effect....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/54A61K31/7068A61P35/00
CPCA61K47/6929A61K47/549A61K31/7068A61P35/00
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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