Industrialized production of liposome combination medicine by molecular dispersion method, and quality control technology

Abstract

The invention discloses industrialized production of a liposome combination medicine by molecular dispersion method, and quality control technology. The liposome combination medicine comprises following raw materials, by molar ratio, 0.03 to 0.15 portion of an active ingredient, 0.40 to 2.20 portions of phospholipid, 0.01 to 0.06 portion of an antioxygen, 1.05 to 2.60 portions of a phospholipid dispersing agent, 1.20 to 3.70 portions of a liposome drug carrier dispersing agent which can be called as excipient, and 0.10 to 0.55 portion of a surfactant. A preparation method of the liposome combination medicine comprises steps of dissolving, ultrafiltration, spray drying, boiling coating, ingredient preparation and freeze drying. The invention also provides the production quality control technology, and a matched equipment combination of the production method. The equipment combination comprises a dissolving tank, an ultrafiltration column, a spray drier, a boiling coating machine, an ingredient preparation tank and a freezer dryer. 20 embodiments of preparation of the liposome combination medicine are also provided.

Description

technical field [0001] The invention relates to a method for preparing a liposome combination medicine in large-scale industrial production. Production of oral formulations of liposomal combination drugs. The implementation process is: excipient dissolution ultrafiltration-excipient spray drying-phospholipid and drug molecule dispersion coating-phospholipid and drug solid dispersion system hydration granulation-nano 1m particle size liposome drug body dispersion system freeze-drying to produce lipid Plastid Combination Drugs. Background technique [0002] The gap between my country's pharmaceutical technology and raw material drug preparation technology and the international advanced level is only within 5 years, and some have reached or exceeded the international advanced level, and the preparation technology is 10-20 years behind the international advanced level. At present, a large number of second-generation common preparations are produced, while third-generation sust...

AI Technical Summary

Problems solved by technology

High-pressure homogenization method and ultrasonic method can control the particle size, but high-energy crushing will damage the raw material medicine; the latter four methods cannot control the particle size, and the particle size distribution is not concentrated, organic solvent residues, leakage, precipitation, coagulation, Quality problems such as phospholipid corruption;

[0005] 3. The existing liposome preparation method makes the encapsulation efficiency of the liposome-combined drug carrier not reach 85%, and each batch fluctuates and changes greatly; the leakage rate is large, and the significance of the liposome-combined drug is lost;

[0006] 4. The production process is troublesome, energy-consuming and time-consuming, equipment investment is large, the prescription and process are not reliable and immature, resulting in uncontrollable, unstable and poor reproducibility of the preparation quality;

[0007] 5. Improper methods of sterilization and depyrogenation, it is difficult to guarantee aseptic and pyrogen-free operation in the whole process, and the lack of a high degree of sterility concept for liposome combination drugs, resulting in the corruption of liposome combination drugs under bacterial erosion, and the encapsulation rate decreases , the leakage rate is increasing, the validity period is extremely short, and the medicinal value is almost lost;

[0008] 6. The number and size of insoluble particles in the injection exceed the standard;

[0009] 7. Most raw materials, phospholipids, excipients, and solvents are selected without national drug quality standards, and new drug certificates and production approval documents cannot be approved even if they have patents. Registration is very difficult and takes a long time;

[0010] 8. Breaking away from the real situation in China, it took nearly 10 years and more than 20 million yuan from the development to the approval of liposome new drug production. Even the best drug invention patents, most companies dare not invest in development

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