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Method for controlling grain diameter of nano-drug carrier

A nano-drug carrier, particle size technology, applied in the field of biomedicine, can solve problems such as reducing stability, reducing particle size, safety impact, etc., and achieving the effect of avoiding the increase of related substances, the reduction of homogenization pressure, and the avoidance of high-pressure operation

Inactive Publication Date: 2014-04-23
SHANGHAI NEW ASIA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] Existing methods for particle size reduction mainly include ultrasound, high-speed shearing, high-pressure homogenization, extrusion, or spray drying or freeze-drying lipid organic solvents, etc., but the above methods have inevitable shortcomings.
[0009] First of all, ultrasound cannot be industrialized, and the repeatability of the laboratory is poor; secondly, high-speed shearing can reduce the particle size, but the high-speed shearing provided by industrialization cannot reach the required particle size, and it is not uniform and the particle size distribution is wide. Reduce stability; moreover, the particle size can be reduced through high-pressure homogenization, and the temperature near the mean value valve can reach 250°C at the moment of high-pressure homogenization. This temperature has a certain impact on heat-sensitive drugs and phospholipids, which will cause high-temperature oxidation. The rate of hydrolysis increases, which increases the content of related substances, which has a certain impact on safety
Finally, extrusion is the most commonly used mode in foreign laboratories, and it is also the most ideal mode. However, for some lipid membrane materials with high phase transition temperature, even high pressure cannot pass through the membrane, and flat filtration is prone to membrane clogging. , frequent membrane changes are prone to contamination
In addition, although spray-drying lipid organic solvents is an ideal model, domestic equipment is still unable to meet the requirements of large-scale production
Freeze-drying lipid organic solvents has restrictions on the types of organic solvents, and the cost is high

Method used

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  • Method for controlling grain diameter of nano-drug carrier
  • Method for controlling grain diameter of nano-drug carrier
  • Method for controlling grain diameter of nano-drug carrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1: Amphotericin B liposome is an active drug-loading liposome, and the mixing ratio of the non-aqueous phase and the aqueous phase is the volume ratio.

[0039]

[0040] The preparation process is as follows:

[0041] Weigh the prescribed amount of hydrogenated soybean lecithin and cholesterol and dissolve them in an appropriate amount of absolute ethanol, and evaporate under reduced pressure to form a lipid film; prepare the water phase according to different two-phase ratios: dissolve amphotericin B with 0.04 M sodium hydroxide, Add sodium deoxycholate and sucrose into the phosphate buffer solution, adjust the pH to 7-8, then mix with the phospholipid membrane to hydrate and homogenize. Use ultrafiltration equipment to concentrate the two-phase ratios of 1:2, 1:4, and 1:6 to 1:1, filter and sterilize four feed solutions, and measure the particle size. For the particle size chart, please refer to the appendix of the instruction manual Figures 1 to 4 . ...

Embodiment 2

[0042] Embodiment 2: Flurbiprofen axetil emulsion is passive drug loading, and the mixing ratio of the two-phase non-aqueous phase and the aqueous phase is the volume ratio.

[0043]

[0044] The preparation process is as follows:

[0045] Heat the prescribed amount of flurbiprofen axetil, refined soybean oil and refined lecithin, stir, dissolve and mix; prepare the water phase according to different two-phase ratios: dissolve glycerin in water for injection, then mix with the non-aqueous phase, fully Emulsify, homogenize. Use ultrafiltration equipment to concentrate the two-phase ratios of 1:2, 1:3, and 1:4 to 1:1, filter and sterilize four feed solutions, and measure the particle size. For the particle size chart, please refer to the appendix of the instruction manual Figures 5 to 8 .

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Abstract

The invention discloses a method for controlling the grain diameter of a nano-drug carrier. The method is convenient and strong in production availability, and can be used for increasing the drug loading capacity. The method for controlling the grain diameter of a nano-drug carrier realizes grain diameter control by regulating the proportion of non-aqueous phase and aqueous phase when the non-aqueous phase and the aqueous phase are mixed in the preparing process, and is combined by concentrating a material by ultrafiltration equipment to restore the proportion of the non-aqueous phase and the aqueous phase to the target proportion. A plurality of drug-loading liposomes prepared by the method are small in grain diameter, high drug loading capacity, high encapsulation efficiency and convenient for industrial production, a new scheme is provided to quality control of nano-drug carriers, and the pace of researching and developing liposome, nano-particle, micelle and other novel preparations can be accelerated.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a method for controlling the particle size of a nano drug carrier. technical background [0002] Nano-drug carriers usually refer to a new type of carrier with a particle size of 10-1000nm, usually made of natural or synthetic polymer materials, such as liposomes, emulsions, solid lipid nanoparticles, nanocapsules, nanospheres, polymers, etc. micelles etc. The main features are that it can improve the solubility and stability of the drug, improve the properties and targeting of the drug, prolong the action time of the drug, increase the curative effect, and reduce the toxicity and side effects. [0003] Capillary endothelial cells in some tissues in the body are discontinuous, and these discontinuous endothelial cell connections have some window structures, and these window structures help nanoparticles enter these tissues through endothelial cells, so as to realize the pene...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K9/107A61K9/51A61K9/14A61K9/19
Inventor 郑玉林陈玉双
Owner SHANGHAI NEW ASIA PHARMA