CN-121987557-A - Alta Lu Lun for treating muscular atrophy and preparation method thereof

CN121987557ACN 121987557 ACN121987557 ACN 121987557ACN-121987557-A

Abstract

The invention relates to the technical field of medicines, and discloses an atta Lu Lun for treating muscular atrophy and a preparation method thereof. The preparation method comprises two main steps of synthesizing the Arga Lu Lun and preparing the drug-loaded nanoparticle gel. The method comprises the steps of mixing the atta Lu Lun with a polyethylene glycol-polylactic acid segmented copolymer and phospholipid to form nano particles, and then mixing the nano particles with a modified cellulose solution to prepare gel. The method solves the problems of bitter taste, frequent administration and poor compliance of the existing Alta Lu Lun oral dosage form, realizes long-acting injection administration, and reduces administration times. The obtained gel has pH response release characteristic, can intelligently release medicine at lesion sites, improves local curative effect, and reduces systemic exposure and side effects.

Inventors

LU CHENGXIAN
XIE LUJIE
LU XIN

Assignees

峨眉山鸿森生物医药股份有限公司

Dates

Publication Date: 20260508
Application Date: 20251212

Claims (7)

1. A method of preparing adalim Lu Lun for the treatment of muscle atrophy, comprising the steps of: Synthesizing an altower Lu Lun, namely dissolving 3-cyanobenzoic acid methyl ester serving as a starting material by adding isopropanol, adding hydroxylamine hydrochloride, stirring at 60 ℃ for reaction, filtering to remove solid waste, recovering a concentrated organic solvent, and drying to obtain an intermediate 1, adding o-fluorobenzoyl chloride and methanol into the intermediate 1, gradually heating to 40 ℃ from 0 ℃ for reaction for 5 hours, filtering to remove the solid waste, recovering a concentrated organic solvent, drying to obtain an intermediate 2, reducing the temperature to 0 ℃, slowly dropwise adding sodium hydroxide into the intermediate 2, heating to 50 ℃ for reaction after dropwise adding, filtering to remove the solid waste, recovering the concentrated organic solvent, drying to obtain an intermediate 3, adding tetrahydrofuran and hydrochloric acid into the intermediate 3, stirring for reaction to generate an altower Lu Lun; the preparation of drug-loaded nano particles comprises the steps of crushing the obtained atta Lu Lun through a 100-mesh sieve, mixing the atta Lu Lun obtained by synthesis with polyethylene glycol-polylactic acid segmented copolymer and phospholipid, dissolving the mixture in acetone, wherein atta Lu Lun accounts for 10% of the mixture in mass ratio, phospholipid accounts for 10-15% of the mixture in mass ratio, the balance of the polyethylene glycol-polylactic acid segmented copolymer is slowly dripped into deionized water under stirring at 250 revolutions per minute, the volume ratio of water phase to organic phase is 10:1, the dripping speed is 1 milliliter per minute, purging the organic solvent for 3 hours by using nitrogen to obtain nano particle dispersion liquid, and centrifuging and purifying; preparing gel, namely re-dispersing the purified drug-loaded nano particles in phosphate buffer salt solution, concentrating to the concentration of 20 weight percent, loading into a syringe, and mixing the modified cellulose solution and the drug-loaded nano particle dispersion liquid through a static mixer to obtain the alpha Lu Lun gel.
2. The method of claim 1, wherein the phospholipid is soybean phosphate and comprises 15% of the mixture by mass.
3. A method of preparing attomoto Lu Lun for the treatment of muscle wasting according to claim 1, wherein the phospholipid comprises soybean phosphate and dipalmitoyl phosphatidylglycerol, wherein soybean phosphate comprises 13% of the mixture by mass and dipalmitoyl phosphatidylglycerol comprises 2% of the mixture by mass.
4. The method of preparing atta Lu Lun for the treatment of muscular dystrophy according to claim 1, wherein the phospholipids include hydrogenated soy lecithin, dioleoyl phosphatidylethanolamine and cholesterol hemisuccinate, wherein the hydrogenated soy lecithin comprises 9% by mass of the mixture, the dioleoyl phosphatidylethanolamine comprises 9% by mass of the mixture, and the cholesterol hemisuccinate comprises 10% by mass of the mixture.
5. The method for preparing the attomoto Lu Lun for treating amyotrophy according to claim 1, wherein the modified cellulose solution is dodecyl modified hydroxypropyl methyl cellulose solution, the preparation method comprises the steps of dissolving hydroxypropyl methyl cellulose in N-methyl pyrrolidone, stirring and swelling at 80 ℃, cooling to 25 ℃, adding dodecyl isocyanate and N, N-diisopropylethylamine catalyst, reacting at 25 ℃ for 16 hours, pouring the reaction solution into ethanol water to precipitate, dialyzing, freeze-drying, and dissolving in physiological saline to prepare 50g/L solution.
6. The method of claim 1, wherein the drug-loaded nanoparticle dispersion is mixed with the modified cellulose solution by a sterile line lock static mixer.
7. A method of preparing atta Lu Lun for the treatment of muscular atrophy, wherein said atta Lu Lun is prepared by a method according to any one of claims 1-6.

Description

Alta Lu Lun for treating muscular atrophy and preparation method thereof Technical Field The invention relates to an atta Lu Lun for treating amyotrophy and a preparation method thereof. Background The ara Lu Lun is a small molecule oral medicine, belongs to a code reading medicine, and has a core action mechanism that a ribosome is selectively induced to read through premature but abnormal stop codons, so that a protein which is terminated in advance due to nonsense mutation can complete a synthesis process, thereby recovering part of functions. Is used for bedridden patients aged 2 years and older for treating diseases caused by nonsense mutation of muscular dystrophy protein gene. The attomour Lu Lun is combined with a ribosome to induce the attomour to ignore a stop codon signal, so that a peptide chain is promoted to continue to extend, and finally, the full-length protein with partial functions is generated. The current common administration mode is oral administration, and because patients are more facing children, and the patients have bitter taste, the administration amount is higher, and 3 times a day are needed, therefore, the administration mode which reduces the administration times and improves the compliance is needed, but the dosage form is changed, the degradation is easy to produce impurities, the production process is required to be completely optimized, and the process is simpler and more convenient. Disclosure of Invention The embodiment of the application solves the problems in the prior art by providing the atta Lu Lun for treating muscular atrophy and the preparation method thereof. The embodiment of the application provides a preparation method of attomone Lu Lun for treating amyotrophy, which comprises the following steps: Synthesizing an altower Lu Lun, namely dissolving 3-cyanobenzoic acid methyl ester serving as a starting material by adding isopropanol, adding hydroxylamine hydrochloride, stirring at 60 ℃ for reaction, filtering to remove solid waste, recovering a concentrated organic solvent, and drying to obtain an intermediate 1, adding o-fluorobenzoyl chloride and methanol into the intermediate 1, gradually heating to 40 ℃ from 0 ℃ for reaction for 5 hours, filtering to remove the solid waste, recovering a concentrated organic solvent, drying to obtain an intermediate 2, reducing the temperature to 0 ℃, slowly dropwise adding sodium hydroxide into the intermediate 2, heating to 50 ℃ for reaction after dropwise adding, filtering to remove the solid waste, recovering the concentrated organic solvent, drying to obtain an intermediate 3, adding tetrahydrofuran and hydrochloric acid into the intermediate 3, stirring for reaction to generate an altower Lu Lun; the preparation of drug-loaded nano particles comprises the steps of crushing the obtained atta Lu Lun through a 100-mesh sieve, mixing the atta Lu Lun obtained by synthesis with polyethylene glycol-polylactic acid segmented copolymer and phospholipid, dissolving the mixture in acetone, wherein atta Lu Lun accounts for 10% of the mixture in mass ratio, phospholipid accounts for 10-15% of the mixture in mass ratio, the balance of the polyethylene glycol-polylactic acid segmented copolymer is slowly dripped into deionized water under stirring at 250 revolutions per minute, the volume ratio of water phase to organic phase is 10:1, the dripping speed is 1 milliliter per minute, purging the organic solvent for 3 hours by using nitrogen to obtain nano particle dispersion liquid, and centrifuging and purifying; preparing gel, namely re-dispersing the purified drug-loaded nano particles in phosphate buffer salt solution, concentrating to the concentration of 20 weight percent, loading into a syringe, and mixing the modified cellulose solution and the drug-loaded nano particle dispersion liquid through a static mixer to obtain the alpha Lu Lun gel. Further, the phospholipid is soybean phosphate, and accounts for 15% of the mass of the mixture. Further, the phospholipid comprises soybean phosphate and dipalmitoyl phosphatidyl glycerol, wherein the soybean phosphate accounts for 13% of the mass ratio of the mixture, and the dipalmitoyl phosphatidyl glycerol accounts for 2% of the mass ratio of the mixture. Further, the phospholipids include hydrogenated soybean lecithin, dioleoyl phosphatidylethanolamine and cholesterol hemisuccinate, wherein the hydrogenated soybean lecithin accounts for 9% of the mixture by mass, the dioleoyl phosphatidylethanolamine accounts for 9% of the mixture by mass, and the cholesterol hemisuccinate accounts for 10% of the mixture by mass. Further, the modified cellulose solution is a dodecyl modified hydroxypropyl methyl cellulose solution, and the preparation method comprises the steps of dissolving hydroxypropyl methyl cellulose in N-methylpyrrolidone, stirring and swelling at 80 ℃, cooling to 25 ℃, adding dodecyl isocyanate and N, N-diisopropylethylamine catalyst, reacting for 16 hours at 25 ℃, pouring th