Drug containing tacrine, preparation method for drug, pharmaceutical composition and application of drug
A tacrine and drug technology, applied in the field of its preparation, tacrine-containing drugs, can solve the problems of self-design contradiction between toxicity and transfection activity, difficult connection, non-toxic degradation, difficult to ensure targeting groups, etc.
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[0154] According to the second aspect of the present application, there is also provided a method for preparing the above tacrine-containing drug, which includes the following steps: providing any nucleic acid nanoparticle described above; Tacrine is mounted on nucleic acid nanoparticles to obtain tacrine-containing medicines.
[0155] When physically linked, tacrine is usually intercalated between GC base pairs by physical intercalation. When the covalent link is used for linking, tacrine usually reacts with the amino group outside the G ring to form a covalent link. The drug containing tacrine prepared by the above method can have better targeting after the target head is modified, and can stably deliver tacrine with high reliability.
[0156] In a preferred embodiment, the step of mounting tacrine through physical connection includes: mixing and stirring tacrine, nucleic acid nanoparticles and the first solvent to obtain a premixed system; precipitating the premixed system...
Embodiment 1
[0177] 1. RNA and DNA nanoparticle carriers:
[0178] (1) The base sequences of the three polynucleotides that make up the RNA nanoparticles are shown in Table 1:
[0179] Table 1:
[0180]
[0181] (2) Three polynucleotide base sequences of DNA nanoparticles
[0182] 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.
[0183] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0184] 2. Self-assembly experimental steps:
[0185] (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;
[0186] (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
[0197] 1. Seven groups of short-sequence RNA nanoparticle carriers:
[0198] (1) See Table 2 to Table 8 for the base sequences of the three polynucleotides that make up the RNA nanoparticles in seven groups:
[0199] Table 2: R-1
[0200]
[0201] Table 3: R-2
[0202]
[0203] Table 4: R-3
[0204]
[0205] Table 5: R-4
[0206]
[0207] Table 6: R-5
[0208]
[0209] Table 7: R-6
[0210]
[0211] Table 8: R-7
[0212]
[0213] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0214] 2. Self-assembly experimental steps:
[0215] (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;
[0216] (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;
[0217] (3) Load the product onto an 8% (m / v) non-denat...
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