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Medicine containing oxaliplatin as well as preparation method, pharmaceutical composition and application thereof

An oxaliplatin and drug technology, which is applied in the field of oxaliplatin-containing drugs, can solve the problems of difficult connection, non-toxic degradation, limited delivery reliability of small-molecule drug oxaliplatin, and limited clinical application of oxaliplatin drugs. Problems such as the self-design contradiction between toxicity and transfection activity

Active Publication Date: 2020-04-28
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 su

Method used

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  • Medicine containing oxaliplatin as well as preparation method, pharmaceutical composition and application thereof
  • Medicine containing oxaliplatin as well as preparation method, pharmaceutical composition and application thereof
  • Medicine containing oxaliplatin as well as preparation method, pharmaceutical composition and application thereof

Examples

Experimental program
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Effect test

Example Embodiment

[0154] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned oxaliplatin-containing drug, which includes the following steps: providing any of the above-mentioned nucleic acid nanoparticles; and by means of physical connection and / or covalent connection The oxaliplatin is mounted on nucleic acid nanoparticles to obtain a drug containing oxaliplatin.

[0155] When physical connection is used, oxaliplatin is usually inserted between GC base pairs in a physical intercalation form. When a covalent connection is used for connection, oxaliplatin usually chemically reacts with the amino group outside the G ring to form a covalent connection. The oxaliplatin-containing medicine prepared by the above-mentioned method has good targeting ability after modification of the target head, can deliver oxaliplatin stably, and has high reliability.

[0156] In a preferred embodiment, the step of mounting oxaliplatin by means of p...

Example Embodiment

[0178] Example 1

[0179] 1. RNA and DNA nanoparticle carrier:

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

[0181] Table 1:

[0182]

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

[0184] DNA uses the same sequence as the above RNA, 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.

[0185] The a, b, and c strands of the aforementioned RNA nanoparticles and DNA nanoparticles are all commissioned to synthesize by Sangong Bioengineering (Shanghai) Co., Ltd.

[0186] 2. Self-assembly experiment steps:

[0187] (1) Mix RNA or DNA single strands a, b, and c 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 (where the RNA assembly temperature is 80°C and the DNA assembly temperature is 95°C), hold it for 5 minutes a...

Example Embodiment

[0198] Example 2

[0199] 1. 7 groups of short-sequence RNA nanoparticle carriers:

[0200] (1) The base sequences of the three polynucleotides that make up the 7 groups of RNA nanoparticles are shown in Tables 2 to 8 respectively:

[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 are all commissioned by Shenggong Bioengineering (Shanghai) Co., Ltd. to synthesize.

[0216] 2. Self-assembly experiment steps:

[0217] (1) Mix RNA single strands a, b, and c 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 5 minutes, and then slowly lower the temperature to room temperature at a rate of 2°C / min;

[0219] (3) Load the product on an 8% (m / v) non-denaturing PAGE gel and purify th...

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Abstract

The application provides a medicine containing oxaliplatin as well as a preparation method, a pharmaceutical composition and application thereof. The medicine comprises nucleic acid nanoparticles andoxaliplatin, wherein the oxaliplatin is mounted on the nucleic acid nanoparticles. The nucleic acid nanoparticle comprises a nucleic acid structural domain including a sequence a, a sequence b and a sequence c; the sequence a comprises a sequence a1 or a sequence in which at least one base is inserted, deleted or replaced in the sequence a1, the sequence b comprises a sequence b1 or a sequence inwhich at least one base is inserted, deleted or replaced in the sequence b1, and the sequence c comprises a sequence c1 or a sequence in which at least one base is inserted, deleted or replaced in thesequence c1. According to the oxaliplatin-containing medicine provided by the invention, the nucleic acid structural domain of the is modified by the target head, so that the good targeting propertyis realized; oxaliplatin can be delivered stably; and the reliability is high.

Description

technical field [0001] The application relates to the field of medicine, in particular, to a medicine containing oxaliplatin, its preparation method, pharmaceutical composition and application. Background technique [0002] Oxaliplatin (Oxaliplatin) is a third-generation platinum anticancer drug, a platinum compound of diaminocyclohexane, that is, the amino group of cisplatin is replaced by a 1,2-diaminocyclohexane group. Similar to other platinum-based drugs, they all target DNA, and platinum atoms form cross-links with DNA to antagonize its replication and transcription. It has a good curative effect on colorectal cancer and ovarian cancer, and has certain curative effect on gastric cancer, non-Hodgkin's lymphoma, non-small cell carcinoma, and head and neck tumors. [0003] Currently, antitumor antibiotics, including oxaliplatin, must be administered in large doses of chemotherapy drugs in order to achieve effective therapeutic levels at the tumor site, but systemic admin...

Claims

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Application Information

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IPC IPC(8): A61K47/26A61K47/54A61K31/555A61P35/00
CPCA61K47/26A61K47/549A61K31/555A61P35/00
Inventor 王力源王萌
Owner BAI YAO ZHI DA BEIJING NANOBIO TECH CO LTD
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