Device and method for preparing vesica with inner and outer water phase gradient difference

A technology with poor gradient and vesicles is applied in the field of pharmaceutical preparations to achieve the effects of improving the liquid separation process, increasing the filtration speed, and being convenient to operate.

Inactive Publication Date: 2013-01-02
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0022] Aiming at the problems of difficult quality control, long time-consuming, low gradient, high cost, and difficulty in large-scale production in the process of establishing the internal and external aqueous phase gradient of liposomes , the present invention designs a method and corresponding device that can quickly and large-scale prepare vesicles / liposomes with a gradient difference between the inner and outer water phases

Method used

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  • Device and method for preparing vesica with inner and outer water phase gradient difference
  • Device and method for preparing vesica with inner and outer water phase gradient difference

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0128] Example 1 Dialysis method and filtered ion exchange method were used to establish ammonium sulfate gradient for liposomes and load drugs

[0129] Prescription HSPC 4.5g

[0130] CH 1.5g

[0131] PEG-CHS 1.5g

[0132] Hydration medium: 150 mL of 200 mmol ammonium sulfate solution.

[0133] Prepare blank liposomes: Weigh the prescribed amount of HSPC, CH, PEG-CHS (PEG molecular weight is 2000), and dissolve the membrane material with 12 mL of ethanol at 55°C to obtain the lipid phase; hydrate it before heating to 55°C The medium is injected into the lipid phase and incubated for 10 minutes to prepare the primary liposomes. After 20,000 psi high pressure homogenization treatment, the liposomes are reduced to 100 nm in size, and then passed through 0.8, 0.45, and 0.22 μm microporous membranes. , That is, a blank liposome is obtained.

[0134] Dialysis method to establish a gradient: take 1.0 mL blank liposomes, 250 mL 5% ( w / v ) Xylitol solution is the dialysis medium (1:250, v / v)...

Embodiment approach

[0135] Filtration ion exchange method to establish gradient: attached figure 2 An embodiment according to the present invention is given: the membrane separation device (1) in this embodiment is a hollow fiber membrane module (polyethersulfone with a water bath temperature control device, a molecular weight cut-off of 100K Da, and a membrane area of ​​1.5 m). 2 ); The ion exchange device (2) in this embodiment is a chromatographic column with a constant temperature device; the ion exchanger in the chromatographic column is a mixture of S 100 type cation exchange resin and M 800 type anion exchange resin ( v / v =1 / 1, depending on the wet volume), the exchange capacity of the mixed ion exchange resin used is 12 times the theoretical required exchange capacity; the dialysis medium is 5% ( w / v ) Xylitol solution, the volume ratio of dialysis medium to blank liposome is 10:1; the vesicle suspension pump (5) and dialysis medium pump (6) used are medical peristaltic pumps.

[0136] ste...

Embodiment 2

[0149] take" Example 1 "Blank liposome 50 mL, with a mixture of ZB-1 cation exchange fiber and ZB-2 anion exchange fiber ( v / v =1 / 1, depending on the wet volume) is a mixed ion exchanger, the exchange capacity of the mixed ion exchange fiber used is 3 times the theoretical required exchange capacity; the dialysis medium is isotonic sucrose solution, the volume of the dialysis medium and the blank liposome The ratio is 15:1; the establishment and operation steps of the gradient device are the same as in "Example 1". The obtained gradient liposomes are loaded with epirubicin, doxorubicin and mitoxantrone (the weight ratio of drug to HSPC is 1:10), and the encapsulation efficiency is higher than 95%.

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Abstract

The invention belongs to the field of a pharmaceutical preparation and discloses a method and a device for rapidly preparing a vesica (including liposome) with inner and outer water phase gradient difference in a large scale, and an application thereof. According to the device and the method disclosed by the invention, a membrane separation mechanism, and an ion exchanging and adsorption mechanism are ingeniously combined; and when the property, the ion gradient type and the preparation scale of the vesica with the needed gradient are different, a membrane separation device and an ion exchanging device, which have the different performances, are combined. With the adoption of a membrane separation method, cations, anions, zwitter ions and / or charge macromolecular substances in a vesica mixed suspension hydrated medium are distributed into a dialysis medium; and an ion exchanging method is used for selectively exchanging or cleaning the cations, the anions, the zwitter ions and / or the charge macromolecular substances in the dialysis medium, so that the vesica can establish the greater inner and outer water phase gradient difference in shorter time. The method and the device can be applied to preparing liposome gel, magnetic liposome, and nano grain / nano gel.

Description

Technical field: [0001] The invention belongs to the field of pharmaceutical preparations, and discloses a method and a related device capable of rapidly and large-scale preparation of vesicles (including liposomes) with a gradient difference between internal and external water phases. The invention also provides applications of the vesicles. Background technique: [0002] Some amphiphilic molecules, such as many natural or synthetic surfactants and phospholipids that cannot simply associate into micelles, will spontaneously form a molecular orderly assembly with a closed double-layer structure when dispersed in water, called Vesicles (vesicles), also known as liposomes (liposomes). The meaning of the terms vesicle and liposome is somewhat ambiguous in the literature. It is generally believed that if these amphiphilic molecules are composed of synthetic surfactants, the formed structures are called vesicles; if they are composed of natural surfactant lecithin, they are ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61J3/00
Inventor 邓意辉佘振南程晓波杨强何琳徐洋翟文君
Owner SHENYANG PHARMA UNIVERSITY
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