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

A drug, cisplatin technology, applied in the field of medicine, can solve the problems of the small molecule drug cisplatin delivery reliability, the limited clinical application of cisplatin drugs, the contradiction between toxicity and transfection activity, the difficulty of connection and non-toxic degradation, etc., to achieve The effect of high reliability, improved stability, and reduced 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 cisplatin is one of the difficulties in solving the current limited clinical application of cisplatin.

Method used

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  • Cisplatin-containing medicine, preparation method, pharmaceutical composition and application thereof
  • Cisplatin-containing medicine, preparation method, pharmaceutical composition and application thereof
  • Cisplatin-containing medicine, preparation method, 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 cisplatin-containing medicine, which comprises the following steps: providing any of the above-mentioned nucleic acid nanoparticles; Platinum is mounted on nucleic acid nanoparticles to obtain cisplatin-containing drugs.

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

[0158] In a preferred embodiment, the step of mounting cisplatin by physical connection includes: mixing and stirring cisplatin, nucleic acid nanoparticles and a first sol...

Embodiment 1

[0181] 1. RNA and DNA nanoparticle carriers:

[0182] (1) The base sequences of the three polynucleotides constituting the RNA nanoparticles are shown in Table 1:

[0183] Table 1:

[0184]

[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 ...

Embodiment 2

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

[0203] (1) The base sequences of the three polynucleotides that make up the 7 groups of RNA nanoparticles are shown in Tables 2 to 8:

[0204] Table 2: R-1

[0205]

[0206] Table 3: R-2

[0207]

[0208] Table 4: R-3

[0209]

[0210] Table 5: R-4

[0211]

[0212] Table 6: R-5

[0213]

[0214] Table 7: R-6

[0215]

[0216] Table 8: R-7

[0217]

[0218] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0219] Second, the self-assembly experimental steps:

[0220] (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;

[0221] (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;

[0222] (3) Load the product onto an 8% (m / v...

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Abstract

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

Description

technical field [0001] The present application relates to the field of medicine, in particular, to a cisplatin-containing medicine, its preparation method, pharmaceutical composition and application. Background technique [0002] Cisplatin (Cisplatin, referred to as DDP, CSA: 15773-27-1, molecular formula: Cl 2 H 4 N 2 PtI, molecular weight: 298.029) is orange-yellow or yellow crystalline powder, slightly soluble in water, easily soluble in methylformamide. It can be gradually converted to trans or hydrolyzed in aqueous solution. It is clinically used in various solid tumors such as ovarian cancer, prostate cancer, testicular cancer, lung cancer, nasopharyngeal cancer, esophageal cancer, malignant lymphoma, head and neck squamous cell carcinoma, thyroid cancer and osteosarcoma. [0003] Currently, antitumor drugs, including cisplatin, must be administered in large doses of chemotherapeutic drugs in order to achieve effective therapeutic levels at the tumor site. However,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/54A61K47/55A61K9/51A61K47/26A61K33/243A61P35/00
CPCA61K47/6929A61K47/549A61K47/55A61K9/5123A61K33/24A61P35/00
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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