Paclitaxel-containing medicine, and preparation method, pharmaceutical composition and application thereof
A paclitaxel and drug technology, applied in the field of medicine, can solve problems such as the contradiction between toxicity and transfection activity, the difficulty of non-toxic degradation of the connection, and the difficulty of ensuring the targeting group.
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[0156] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned paclitaxel-containing drug, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; Loaded on nucleic acid nanoparticles to obtain paclitaxel-containing drugs.
[0157] When physically linked, paclitaxel is usually intercalated between GC base pairs by physical intercalation. In the case of covalent linkage, paclitaxel usually undergoes a chemical reaction with the amino group outside the G ring to form a covalent linkage. The paclitaxel-containing drug prepared by the above method can have better targeting after the target head is modified, and can stably deliver paclitaxel with high reliability.
[0158] In a preferred embodiment, the step of mounting paclitaxel through physical connection includes: mixing and stirring paclitaxel, nucleic acid nanoparticles and the first solvent to obtain a premi...
Embodiment 1
[0183] 1. RNA and DNA nanoparticle carriers:
[0184] (1) The base sequences of the three polynucleotides that make up 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 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.
[0190] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0191] 2. Self-assembly experimental steps:
[0192] (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;
[0193](2) Heat the mixed solution to 80°C / 95°C (the RNA assembly temperature is 80°C, and the DNA assembly tempera...
Embodiment 2
[0204] 1. Seven groups of short-sequence RNA nanoparticle carriers:
[0205] (1) The base sequences of the three polynucleotides of the seven groups of RNA nanoparticles are shown in Table 2 to Table 8:
[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] 2. Self-assembly experimental steps:
[0224] (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;
[0225] (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;
[0226] (3) Load the product onto an...
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