Medicine containing pentafluorouracil, its preparation method, pharmaceutical composition and application
A pentafluorouracil and drug technology, applied in the field of pentafluorouracil-containing drugs, can solve the problem of the small molecule drug pentafluorouracil delivery reliability, the limited clinical application of pentafluorouracil drugs, the self-design contradiction between toxicity and transfection activity, and the difficulty in ensuring targeting bases. Group and other problems, to achieve the effect of high reliability, improve stability, and reduce the chance of 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 pentafluorouracil-containing medicine, comprising the following steps: providing any of the above-mentioned nucleic acid nanoparticles; Fluorouracil is mounted on nucleic acid nanoparticles to obtain a medicine containing pentafluorouracil.
[0155] When physically linked, pentafluorouracil is usually physically intercalated between GC base pairs. When the covalent connection is used for connection, pentafluorouracil usually undergoes a chemical reaction with the amino group outside the G ring to form a covalent connection. The pentafluorouracil-containing medicine prepared by the above-mentioned method has good targeting ability after modification of the target head, can deliver pentafluorouracil stably, and has high reliability.
[0156] In a preferred embodiment, the step of mounting pentafluorouracil by physical connection includes: mixing an...
Embodiment 1
[0179] 1. RNA and DNA nanoparticle carriers:
[0180] (1) The three polynucleotide base sequences that make up the RNA nanoparticle are specifically shown in Table 1:
[0181]
[0182]
[0183] (2) Three polynucleotide base sequences of DNA nanoparticles.
[0184] 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.
[0185] The a, b and c chains of the above RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0186] Second, the self-assembly experimental steps:
[0187] (1) Dissolve 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) Heating the mixed solution to 80°C / 95°C (wherein the RNA assembly temperature is 80°C and the DNA assembly temperature is 95°C), and aft...
Embodiment 2
[0199] 1. 7 groups of short-sequence RNA nanoparticle carriers:
[0200] (1) 7 groups of three polynucleotide base sequences that make up RNA nanoparticles:
[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] Second, the self-assembly experimental steps:
[0217] (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;
[0218] (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;
[0219] (3) Load the product onto an 8% (m / v) native PAGE gel and purify the com...
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