Process for the production of lipidic vehicles

A lipid carrier and liposome technology, applied in the field of producing lipid carriers, can solve the problems of unsatisfactory carrier size and polydispersity index, large amount of resources, complexity and the like

Pending Publication Date: 2020-10-16
NIKOLAOS A FIKIORIS KAI SIA ETAIREIA PERIORISMENIS EFTHINIS WITH DISTINGUISHING TITLE IN TOUCH HEALTH EPE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these solvents represent a safety and health hazard, and it is desirable to avoid their use
Furthermore, many prior art methods are complex and / or require significant resources, time and effort
In addition, the size and polydispersity index of supports obtained by most of the prior art methods are unsatisfactory and thus require additional steps such as ultrafiltration

Method used

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  • Process for the production of lipidic vehicles
  • Process for the production of lipidic vehicles
  • Process for the production of lipidic vehicles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] HSPC: Preparation of stearylamine liposomes

[0057] HSPC (30.0 mg) and stearylamine (0.3 mg) in a molar ratio of 9:0.25 were weighed and placed in a large spherical flask. 3 mL of pure water with dissolved glycerol 20 / 15 / 10% v / v was added to the flask and the mixture was vortexed briefly. A magnet was placed in a silicone oil bath, and the mixture was heated at 60° C. while stirring at 700 rpm for 1 hour. Then, under the same stirring, the suspension was heated at 90° C. for 1 hour. The resulting suspension was cooled to room temperature at a rate of 3 °C / min and a 50 uL sample was extracted which was diluted with 2950 uL of HPLC-grade water and measured by photon correlation spectroscopy (PCS) to calculate the size of the liposomes , polydispersity and zeta-potential. Then, the suspension was heated at 90° C. and 700 rpm for 1 hour, and after cooling, a 50 uL sample was measured again. The results of the prepared liposomes are shown in Table 1, while the size dist...

Embodiment 2

[0068] Preparation of eggPC:cholesterol:stearylamine liposomes

[0069] EggPC (30.0 mg), cholesterol (0.8 / 3.0 mg) and stearylamine (0.3 mg) in a molar ratio of 9:0.5:0.25 or 9:1.8:0.25 were weighed and placed in a large spherical flask. 3 mL of pure water with dissolved glycerol 20% v / v was added to the flask, and the mixture was vortexed for a brief period. A magnet was placed in a silicone oil bath, and the mixture was heated at 60° C. while stirring at 700 rpm for 1 hour. Then, the suspension was heated at 90° C. for 2 hours under the same stirring. The resulting suspension was cooled to room temperature at a rate of 3°C / min, and a 50 uL sample was extracted, diluted with 2950 uL HPLC-grade water and measured with PCS to calculate liposome size and polydispersity. The results of the prepared liposomes are shown in Table 2, while the size distribution of strength, volume and number of particles using 1.8 cholesterol molar ratio is shown in Table 2. figure 2 As shown in ,...

Embodiment 3

[0079] Physical Stability of Liposomes Prepared by the Method of the Invention

[0080] Liposomes containing HSPC:stearylamine 9:0.25, eggPC:cholesterol:stearylamine 9:1.8:0.25 and DSPC:stearylamine 9:0.25 were developed and determined by measuring their size and polydispersity using PCS. Their physical / colloidal stability was assessed for a period of approximately 30 days.

[0081] Weigh HSPC (30.0mg) and stearylamine (0.3mg) of molar ratio 9:0.25, eggPC (30.0mg), cholesterol (3.0mg) and stearylamine (0.3mg) of molar ratio 9:1.8:0.25 and DSPC (30.0 mg) and stearylamine (0.3 mg) in a molar ratio of 9:0.25 and placed in a separate large spherical flask. 3 mL of pure water with dissolved glycerol 20% v / v was added to the flask, and the mixture was vortexed for a brief period of time. A magnet was placed in a silicone oil bath, and the mixture was heated at 60° C. while stirring at 700 rpm for 1 hour. Then, under the same stirring, the suspension was heated at 90° C. for 1 hou...

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Abstract

Process for the production of lipidic vehicles comprising providing a mixture of an amphiphilic lipid and a promoter in a liquid medium comprising water and a liquid polyol, stirring and heating the mixture in two heating steps, wherein the temperature of the second heating step is higher than the temperature of the first heating step and allowing the mixture to cool down to room temperature.

Description

technical field [0001] The present invention relates to methods for producing lipid carriers, such as liposomes. Background technique [0002] Lipid bioactive ingredient delivery system [0003] Lipid-based delivery systems for bioactive ingredients have shown great potential for the delivery of poorly water-soluble bioactive ingredients such as mainly lipophilic drugs and several successfully marketed products. The lipid carrier structure (e.g. bilayer, cubic, hexagonal, etc.) depends on the concentration of phospholipids / lipids involved in the process and their geometry, which is related to their chemical structure (D. Papahadjopoulos, J.C. Watkins, Phospholipid model membrane, Permeability properties of hydrated liquid crystals, Biochim.Biophys.Acta 135,639(1967); J.Milhaud, New insights into water-phospholipid model membrane interactions, Biochim.Biophys.Acta1663,19(2004); D.D.Lasic, et al., Spontaneousvesiculation, Adv. Colloid. Interface Sci. 89-90, 337 (2001)). Thu...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): A61K9/127A61K9/19A61K31/12
CPCA61K9/127A61K9/1277A61K9/19A61K31/12A61K45/06
InventorN·纳齐里斯A-G·皮帕C·德米特佐斯
OwnerNIKOLAOS A FIKIORIS KAI SIA ETAIREIA PERIORISMENIS EFTHINIS WITH DISTINGUISHING TITLE IN TOUCH HEALTH EPE