Lenalidomide-containing medicine, and preparation method, pharmaceutical composition and application thereof
A technology of lenalidomide and drugs, which is applied in the direction of drug combination, medical preparations containing active ingredients, drug delivery, etc., can solve the problem of limited clinical application, influence, toxicity and reliability of small molecule drug lenalidomide delivery Contradictions in the design of transfection activity itself
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[0155] According to the second aspect of the present application, there is also provided a method for preparing the above-mentioned lenalidomide-containing drug, 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 lenalidomide is mounted on the nucleic acid nanoparticles to obtain the lenalidomide-containing drug.
[0156] When physically linked, lenalidomide typically intercalates physically between GC base pairs. However, when covalent linkage is used for linkage, lenalidomide usually reacts with the amino group outside the G ring to form a covalent linkage. The lenalidomide-containing drug prepared by the above-mentioned method can have better targeting after the target head is modified, can deliver lenalidomide stably, and has high reliability.
[0157] In a preferred embodiment, the step of mounting lenalidomide through physical connection includes: mixing ...
Embodiment 1
[0182] 1. RNA and DNA nanoparticle carriers:
[0183] (1) The base sequences of the three polynucleotides that make up the RNA nanoparticles are shown in Table 1:
[0184] Table 1:
[0185]
[0186]
[0187] (2) Three polynucleotide base sequences of DNA nanoparticles
[0188] 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.
[0189] The a, b, and c strands of the above-mentioned RNA nanoparticles and DNA nanoparticles were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0190] 2. Self-assembly experimental steps:
[0191] (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;
[0192] (2) Heat the mixed solution to 80°C / 95°C (the RNA assembly temperature is 80°C, and the DNA assembly temperat...
Embodiment 2
[0203] 1. Seven groups of short-sequence RNA nanoparticle carriers:
[0204] (1) The base sequences of the three polynucleotides of the seven groups of RNA nanoparticles are shown in Table 2 to Table 8:
[0205] Table 2: R-1
[0206]
[0207] Table 3: R-2
[0208]
[0209]
[0210] Table 4: R-3
[0211]
[0212] Table 5: R-4
[0213]
[0214] Table 6: R-5
[0215]
[0216]
[0217] Table 7: R-6
[0218]
[0219] Table 8: R-7
[0220]
[0221] The single strands of the above seven groups of short-sequence RNA nanoparticle carriers were all synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.
[0222] 2. Self-assembly experimental steps:
[0223] (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;
[0224] (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;
[0225] (3) Load the product onto an...
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