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Cisplatin-containing medicine, preparation method of cisplatin-containing medicine, medicine composition and application of cisplatin-containing medicine

A drug, cisplatin technology, applied in the field of medicine, can solve the problems of impact, reliability of small molecule drug cisplatin delivery, limited clinical application of cisplatin, toxicity and self-design contradiction of transfection activity, etc.

Active Publication Date: 2020-05-15
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 of cisplatin-containing medicine, medicine composition and application of cisplatin-containing medicine
  • Cisplatin-containing medicine, preparation method of cisplatin-containing medicine, medicine composition and application of cisplatin-containing medicine
  • Cisplatin-containing medicine, preparation method of cisplatin-containing medicine, medicine composition and application of cisplatin-containing medicine

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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 drug, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; Platinum is mounted on nucleic acid nanoparticles to obtain cisplatin-containing drugs.

[0157] When physically linked, cisplatin typically intercalates physically between GC base pairs. When the covalent link is used for linking, cisplatin usually reacts with the amino group outside the G ring to form a covalent link. The cisplatin-containing drug prepared by the above method can have better targeting after the target head is modified, can stably deliver cisplatin, and has high reliability.

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

Embodiment 1

[0181] 1. RNA and DNA nanoparticle carriers:

[0182] (1) The base sequences of the three polynucleotides that make up 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 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.

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

[0189] 2. Self-assembly experimental steps:

[0190] (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;

[0191] (2) Heat the mixed solution to 80°C / 95°C (the RNA assembly temperature is 80°C, and the DNA assembly temper...

Embodiment 2

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

[0203] (1) See Table 2 to Table 8 for the base sequences of the three polynucleotides that make up the RNA nanoparticles in seven groups:

[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] 2. Self-assembly experimental steps:

[0220] (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;

[0221] (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;

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

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Abstract

The invention provides a cisplatin-containing medicine, a preparation method of the cisplatin-containing medicine, a medicine composition and application. The medicine comprises a nucleic acid nanoparticle and cisplatin mounted on the nucleic acid nanoparticle; and the nucleic acid nanoparticle comprises a nucleic acid structural domain, the nucleic acid structural domain comprises a sequence a, asequence b and a sequence c, the sequence a comprises a sequence a1 or a sequence obtained after insertion, deletion or substitution of at least one base of the sequence a1, the sequence b comprisesa sequence b1 or a sequence obtained after insertion, deletion or substitution of at least one base of the sequence b1, and the sequence c comprises a sequence c1 or a sequence obtained after insertion, deletion or substitution of at least one base of the sequence c1. After target head modification, the nucleic structural domain of the cisplatin-containing medicine has better targeting ability, can stably deliver cisplatin and has high reliability.

Description

technical field [0001] The 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 or yellow crystalline powder, slightly soluble in water, easily soluble in methylformamide. It can be gradually converted into trans or hydrolyzed in aqueous solution. It is clinically effective for 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 osteogenic sarcoma. [0003] Currently, antineoplastic drugs including cisplatin must be administered with high doses of chemotherapy drugs in order to achieve effective therapeutic levels at the tumor site, but syste...

Claims

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Application Information

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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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