Medicine containing vincristine, its preparation method, pharmaceutical composition and application thereof
A vincristine and drug technology, applied in the field of medicine, can solve the limited clinical application of vincristine drug delivery reliability of small molecule drug vincristine, the self-design contradiction between toxicity and transfection activity, difficult connection and non-toxic degradation, etc. problems, to achieve the effect of high reliability, improved stability, and reduced opportunities for contact
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[0154] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned vincristine-containing drug, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; The vincristine is loaded on the nucleic acid nanoparticles to obtain the vincristine-containing medicine.
[0155] When physically linked, vincristine is usually intercalated between GC base pairs by physical intercalation. When the covalent link is used for linking, vincristine usually reacts with the amino group outside the G ring to form a covalent link. The vincristine-containing drug prepared by the above method can have better targeting after the target head is modified, can deliver vincristine stably, and has high reliability.
[0156] In a preferred embodiment, the step of mounting vincristine through physical connection includes: mixing and stirring vincristine, nucleic acid nanoparticles and the first so...
Embodiment 1
[0179] 1. RNA and DNA nanoparticle carriers:
[0180] (1) The base sequences of the three polynucleotides that make up the RNA nanoparticles are shown in Table 1:
[0181] Table 1:
[0182]
[0183] (2) Three polynucleotide base sequences of DNA nanoparticles
[0184] 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.
[0185] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0186] 2. Self-assembly experimental steps:
[0187] (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;
[0188] (2) Heat the mixed solution to 80°C / 95°C (the RNA assembly temperature is 80°C, and the DNA assembly temperature is 95°...
Embodiment 2
[0199] 1. Seven groups of short-sequence RNA nanoparticle carriers:
[0200] (1) The base sequences of the three polynucleotides of the seven groups of RNA nanoparticles are shown in Table 2 to Table 8:
[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 were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0216] 2. Self-assembly experimental steps:
[0217] (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;
[0218] (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;
[0219] (3) Load the product onto an 8% (m / v) non-denaturing...
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