Liraglutide sustained-release microsphere preparation and preparation method thereof

A slow-release microsphere preparation, the technology of liraglutide, applied in the field of biomedicine, can solve the problem of low encapsulation efficiency of liraglutide sustained-release microspheres, difficulty in determining the formulation of sustained-release preparations, and inactivation of liraglutide and other problems, to achieve the effect of uniform particle size, round surface and good stability

Inactive Publication Date: 2015-03-04
浙江美华鼎昌医药科技有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] 2. The commonly used carrier poly(lactic-co-glycolic acid) copolymer (PLGA) is easy to cause local acidification during the degradation process in the body, causing the aggregation of liraglutide, leading to inactivation, and toxicity in severe cases;
[0007] 3. Liraglutide sustained-release microspheres prepared by conventional methods have the disadvantages of low encapsulation efficiency, poor drug loading and severe burst release;
[0008] 4. It is difficult to determine the prescription of sustained-release formulations

Method used

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  • Liraglutide sustained-release microsphere preparation and preparation method thereof
  • Liraglutide sustained-release microsphere preparation and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0042] (1) Pretreatment: The liraglutide API is in a freeze-dried powder state, and the impurities in the analysis and detection content meet the USP requirements and then refrigerated for later use;

[0043] (2) Dissolve 30mg of liraglutide in 1ml of water for injection, and add 3mg of lysine at the same time to prepare the inner water phase; the mass-volume concentration of liraglutide in the inner water phase is 30mg / mL, and lysine The solubility of the acid in the internal aqueous phase is 3%;

[0044] (3) Dissolve 100 mg of poly(lactic-co-glycolic acid) copolymer (the ratio of polylactic acid to glycolic acid in the poly(lactic-co-glycolic acid) copolymer is 1:1, Mw=15000) in 2ml of dichloromethane to obtain an oil phase; The mass-volume concentration of lactic acid glycolic acid copolymer in oil phase is 300mg / mL;

[0045] (4) Mix the inner water phase in step (2) with the oil phase in step (3), and mix and sonicate for 30s under a 100w sonicator to obtain colostrum W ...

Embodiment 2

[0049](1) Pretreatment: The liraglutide API is in a freeze-dried powder state, and the impurities in the analysis and detection content meet the USP requirements and then refrigerated for later use;

[0050] (2) Dissolve 40mg of liraglutide in 1ml of water for injection, and add 8mg of glycine at the same time to obtain the inner water phase; the mass-volume concentration of liraglutide in the inner water phase is 40mg / mL, and glycine in the inner water The mass-volume concentration in the phase is 8 mg / ml;

[0051] (3) Dissolve 300mg of poly(lactic-co-glycolic acid) copolymer (the ratio of polylactic acid to glycolic acid in the poly(lactic-co-glycolic acid) copolymer is 3:1, Mw=10000) in 4ml of dichloromethane to obtain an oil phase; The mass-volume concentration of lactic acid glycolic acid copolymer in oil phase is 300mg / mL;

[0052] (4) Mix the inner water phase in step (2) and the oil phase in step (3), and mix and sonicate for 10 seconds under a 200w ultrasonic breaker...

Embodiment 3

[0056] (1) Pretreatment: The liraglutide API is in a freeze-dried powder state, and the impurities in the analysis and detection content meet the USP requirements and then refrigerated for later use;

[0057] (2) Dissolve 60mg of liraglutide in 1ml of water for injection, and add 30mg of histidine at the same time to prepare the inner water phase; the mass-volume concentration of liraglutide in the inner water phase is 60mg / mL, histidine The solubility of the acid in the internal aqueous phase is a mass-volume concentration of 30 mg / ml;

[0058] (3) Dissolve 500mg of poly(lactic-co-glycolic acid) copolymer (the ratio of polylactic acid to glycolic acid in the poly(lactic-co-glycolic acid) copolymer is 1:3, Mw=15000) in 5ml of dichloromethane to obtain an oil phase; The mass-volume concentration of lactic acid glycolic acid copolymer in oil phase is 300mg / mL;

[0059] (4) Mix the inner water phase in step (2) and the oil phase in step (3), and mix and sonicate for 10 seconds u...

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Abstract

The invention relates to a liraglutide sustained-release micro sphere preparation and a preparation method thereof. The liraglutide sustained-release microsphere preparation comprises 5mg to 100mg of liraglutide, 0.5mg to 10mg of a protective agent and 50mg to 1000mg of a polylactic acid-glycolic acid copolymer, wherein the protective agent is one or a mixture of a plurality of sucrose, mycose, gelatin, mannitol, glycine, lysine and human serum albumin; the molecular weight of the polylactic acid-glycolic acid copolymer is 5000-20000 Daltons, and the ratio of polylactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 1:3 to 3:1. According to the liraglutide sustained-release microsphere preparation disclosed by the invention, regular microspheres and medicines uniformly distributed in the microspheres can be obtained by just emulsifying and volatizing an organic solvent; processing procedures are simple; operation is simple; good repeatability is realized in preparation; the prepared liraglutide sustained-release microsphere preparations in batches have no remarkable difference; the obtained microspheres are uniform in grain size, narrow in distribution, controllable in grain size, round and orderly in surfaces and low in burst release rate.

Description

technical field [0001] The invention relates to a liraglutide sustained-release microsphere preparation and a preparation method thereof, belonging to the technical field of biomedicine. Background technique [0002] Liraglutide is an analogue of human glucagon-like peptide-1 (GLP-1) developed by Novo Nordisk, which can treat patients with type 2 diabetes. The drug was approved for the first time in 27 European countries in June 2009, approved for marketing in the United States and Japan in January 2010, and approved by SFDA for marketing in my country in March 2011. The dosage form is subcutaneous injection, and it only needs to be injected once a day to exert a good hypoglycemic effect. [0003] The existing liraglutide sustained-release microsphere preparations generally use poly(lactic-co-glycolic acid) (PLGA) as a carrier, and PLGA has good compatibility. Compared with exenatide sustained-release preparations, liraglutide sustained-release preparations The curative ef...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/16A61K38/26A61K47/16A61K47/34A61K47/36A61K47/26A61K47/42A61P3/10A61P3/04
Inventor 王传跃章文星方庆华周春萍
Owner 浙江美华鼎昌医药科技有限公司
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