Drug containing pirarubicin, preparation method for drug, pharmaceutical composition and application of drug
A technology of pirarubicin and drugs, which is applied in the field of drugs containing pirarubicin, can solve the problem of difficult non-toxic degradation of connection, limited clinical application of small molecule drug pirarubicin delivery reliability, toxicity and transfection activity Problems such as self-design contradictions
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[0160] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned drug containing pirarubicin, which includes the following steps: providing any one of the above-mentioned nucleic acid nanoparticles; by means of physical connection and / or covalent connection The pirarubicin is mounted on the nucleic acid nanoparticles to obtain the pirarubicin-containing medicine.
[0161] When physically linked, pirarubicin is usually intercalated between GC base pairs by physical intercalation. And when adopting covalent linking mode to link, pirarubicin will usually react with the amino group outside the G ring to form a covalent link. The pirarubicin-containing medicine prepared by the above-mentioned method can have better targeting after the target head is modified, can stably deliver pirarubicin, and has high reliability.
[0162] In a preferred embodiment, the step of mounting pirarubicin by physical connection includes...
Embodiment 1
[0184] 1. RNA and DNA nanoparticle carriers:
[0185] (1) The base sequences of the three polynucleotides that make up the RNA nanoparticles are shown in Table 1:
[0186] Table 1:
[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 temperature is 95°...
Embodiment 2
[0210] 1. Seven groups of short-sequence RNA nanoparticle carriers:
[0211] (1) The base sequences of the three polynucleotides of the seven groups of RNA nanoparticles are shown in Table 2 to Table 8:
[0212] Table 2: R-1
[0213]
[0214] Table 3: R-2
[0215]
[0216] Table 4: R-3
[0217]
[0218] Table 5: R-4
[0219]
[0220] Table 6: R-5
[0221]
[0222] Table 7: R-6
[0223]
[0224] Table 8: R-7
[0225]
[0226] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0227] 2. Self-assembly experimental steps:
[0228] (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;
[0229] (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;
[0230] (3) Load the product onto an 8% (m / v) non-denaturing...
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