Medicine containing docetaxel, its preparation method, pharmaceutical composition and application
A docetaxel and drug technology, applied in the field of preparation of docetaxel-containing drugs, can solve the problem of limited clinical application, toxicity and translocation of small molecule drug docetaxel delivery reliability Dyeing activity self-design contradictions, difficult connection and non-toxic degradation and other problems, to achieve high reliability, improve stability, and reduce the chance of contact
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[0156] According to the second aspect of the present application, there is also provided a preparation method of the above-mentioned docetaxel-containing medicine, comprising the following steps: providing any of the above-mentioned nucleic acid nanoparticles; by means of physical connection and / or covalent connection Docetaxel is mounted on nucleic acid nanoparticles to obtain a drug containing docetaxel.
[0157]When physically linked, docetaxel is usually physically intercalated between GC base pairs. When the connection is made by covalent connection, docetaxel usually chemically reacts with the amino group outside the G ring to form a covalent connection. The docetaxel-containing medicine prepared by the above-mentioned method can have better targeting after target modification, can deliver docetaxel stably, and has high reliability.
[0158] In a preferred embodiment, the step of mounting docetaxel by physical connection includes: mixing and stirring docetaxel, nucleic ...
Embodiment 1
[0183] 1. RNA and DNA nanoparticle carriers:
[0184] (1) The base sequences of the three polynucleotides constituting the RNA nanoparticles are shown in Table 1:
[0185] Table 1:
[0186]
[0187]
[0188] (2) Three polynucleotide base sequences of DNA nanoparticles
[0189] 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.
[0190] The a, b and c chains of the above RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0191] Second, the self-assembly experimental steps:
[0192] (1) Mix and dissolve RNA or DNA single-stranded a, b, c in DEPC water or TMS buffer at a molar ratio of 1:1:1;
[0193] (2) Heating the mixed solution to 80°C / 95°C (wherein the RNA assembly temperature is 80°C and the DNA assembly temperature ...
Embodiment 2
[0204] 1. 7 groups of short-sequence RNA nanoparticle carriers:
[0205] (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:
[0206] Table 2: R-1
[0207]
[0208] Table 3: R-2
[0209]
[0210]
[0211] Table 4: R-3
[0212]
[0213] Table 5: R-4
[0214]
[0215] Table 6: R-5
[0216]
[0217]
[0218] Table 7: R-6
[0219]
[0220] Table 8: R-7
[0221]
[0222] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0223] Second, the self-assembly experimental steps:
[0224] (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;
[0225] (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;
[0226]...
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