CN-122016582-A - Particle size detection method of enkephalin

Abstract

The invention discloses a particle size detection method of enkephalin, which relates to the technical field of particle size detection and comprises the following steps of dispersing an enkephalin sample in a dispersing agent to form a sample to be detected, carrying out dispersion mixing treatment on the sample to be detected to obtain a pretreated sample, adding the pretreated sample into a sample pool of a laser particle size analyzer, stirring for 10 minutes, starting the laser particle size analyzer to carry out enkephalin particle size detection, and carrying out treatment on the detection sample by an ultrasonic instrument.

Inventors

• QIN QIANG
• LI JUE
• HE GANGMIN
• ZHOU HONGYU
• YANG LI

Assignees

• 江苏德迈药业有限公司

Dates

Publication Date

20260512

Application Date

20260306

Claims (9)

1. 1. The method for detecting the particle size of the enkephalin is characterized by comprising the following steps of: s1, dispersing an enkephalin sample in a dispersing agent to form a sample to be detected; s2, carrying out dispersion mixing treatment on the sample to be detected to obtain a pretreated sample; S3, adding the pretreated sample into a sample cell of a laser particle size analyzer, stirring for 10 minutes, starting the laser particle size analyzer, and detecting the particle size of the enkephalin.
2. 2. The method for detecting the particle size of the enkephalin according to claim 1, wherein the stirring speed of the sample cell of S3 is 500-1200rpm, and the optical concentration is 8% -20%.
3. 3. The method for detecting the particle size of enbufene according to claim 1, wherein the dispersant S1 is an aqueous solution containing at least one of sorbitan fatty acid esters, alcohols, and polyoxyethylene polyoxypropylene ether block copolymers.
4. 4. The method for detecting the particle size of the enkephalin according to claim 3, wherein the sorbitan fatty acid ester is tween or span, the alcohol is ethanol, isopropanol, propylene glycol or glycerol, and the polyoxyethylene polyoxypropylene ether block copolymer is poloxamer.
5. 5. The method for detecting the particle size of the enkephalin according to claim 1, wherein the dispersing agent S1 is a mixed solution of poloxamer 188 and water.
6. 6. The method for detecting the particle size of the enkephalin according to claim 5, wherein the mass concentration of poloxamer 188 in the mixed solution is 0.05% -1%.
7. 7. The method for detecting the particle size of the enkephalin according to claim 1, wherein the dispersing and mixing treatment of S2 is at least one of ultrasonic dispersion, magnetic stirring and shearing dispersion.
8. 8. The method for detecting the particle size of the enkephalin according to claim 1, wherein the mass concentration of the enkephalin in the sample to be detected in S1 is 0.03% -10%.
9. 9. The method for detecting the particle size of the enkephalin according to claim 1, wherein the enkephalin sample S1 is enkephalin bulk drug or enkephalin inhalation suspension.

Description

Particle size detection method of enkephalin Technical Field The invention relates to a particle size detection technology, in particular to a particle size detection method of enkephalin. Background Ensifen (ENSIFENTRINE) is a novel dual phosphodiesterase 3/4 (PDE 3/PDE 4) inhibitor, has dual pharmacological activities of anti-inflammatory and bronchodilatory, and is mainly used for treating asthma and Chronic Obstructive Pulmonary Disease (COPD) clinically. As a drug to be administered by the inhaled route, the particle size distribution of the drug substance and its formulation (e.g., inhaled suspension) is a key quality attribute that directly affects pulmonary deposition efficiency, bioavailability, efficacy stability and safety. The excessive particle size can lead to the fact that the medicine can not effectively reach the action part, agglomeration is easy to be caused when the particle size is too small or the particle size is unevenly distributed, and the accuracy and uniformity of dosage are affected, so that the establishment of an accurate and reliable particle size detection method is important for the production quality control of raw medicines and preparations. Currently, the particle size detection method commonly used in the field mostly adopts a wet dispersion technology, namely, a surfactant solution is used as a dispersion medium, so that particle aggregation is prevented, and the representativeness of detection is ensured. In the prior art, conventional nonionic surfactants such as Tween 20 and the like are often selected to prepare dispersion liquid. However, in practical application, the method has a plurality of obvious defects that firstly, the wetting performance of Tween 20 on Ensifen particles is limited, so that a sample is soaked slowly in a dispersing agent, incompletely dispersed lumps are easy to form, the instantaneity and the accuracy of detection are affected, secondly, a uniform and stable dispersed state of a dispersing system is difficult to realize in practical operation, the fluctuation of a detection result is large, the reproducibility is not ideal, and in addition, the Tween 20 has cytotoxicity and irritation to a certain extent, potential risks are formed on health of experimenters due to long-term contact, and the requirement of the modern medicine quality control on increasingly improved safety and environmental protection is not met. Therefore, aiming at the physicochemical characteristic of the specific compound of the enkephalin, developing a particle size detection method with high dispersion efficiency, safe operation and good result reproducibility is a technical problem to be solved in the field. Disclosure of Invention The invention aims to provide a particle size detection method of enkephalin, which aims to solve the problems of large error and poor repeatability of particle size detection results caused by low dispersion efficiency of enkephalin in the prior art. In order to achieve the above purpose, the invention provides a method for detecting the particle size of enfefene, which comprises the following steps: s1, dispersing an enkephalin sample in a dispersing agent to form a sample to be detected; S2, carrying out dispersion mixing treatment on the sample to be detected to obtain a pretreated sample; S3, adding the pretreated sample into a sample cell of a laser particle size analyzer, stirring for 10 minutes, starting the laser particle size analyzer, and detecting the particle size of the enkephalin. Further, the stirring speed of the sample cell in the step S3 is 500-1200rpm, and the optical concentration is 8% -20%. Further, the dispersant of S1 is an aqueous solution containing at least one of sorbitan fatty acid esters, alcohols, and polyoxyethylene polyoxypropylene ether block copolymers. Further, the sorbitan fatty acid ester is tween or span, the alcohol is ethanol, isopropanol, propylene glycol or glycerin, and the polyoxyethylene polyoxypropylene ether segmented copolymer is poloxamer. Further, the dispersing agent in S1 is a mixed solution of poloxamer 188 and water. Further, the mass concentration of poloxamer 188 in the mixed solution is 0.05% -1%. Further, the dispersion and mixing treatment in S2 is at least one of ultrasonic dispersion, magnetic stirring and shearing dispersion. Further, the mass concentration of the enkephalin in the sample to be detected in the step S1 is 0.03% -10%. Further, the samples of the enkephalin in S1 are enkephalin bulk drugs or enkephalin inhalation suspension. Compared with the prior art, the method for detecting the particle size of the enkephalin provided by the invention has the advantages that the ultrasonic instrument is used for processing the detection sample, so that the enkephalin is completely immersed into the medium before detection, and the problems of large detection result error and poor reproducibility caused by low immersion speed of the enkephalin in the sample cell are avoided;