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Lipid microvesicle ultrasound angiography powder agent internally containing mixture gas of fluorine carbon/nitrogen gas and production of the same

A lipid microbubble and fluorocarbon technology, applied in echo/ultrasonic imaging agents and other directions, can solve the problems of unavoidable damage of microbubbles and inability to obtain microbubbles, and achieve the effects of no toxic side effects, improved ability and stable performance

Inactive Publication Date: 2008-02-27
CHONGQING RUNQI PHARMA TECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] To sum up, the prior art mainly adopts acoustic vibration method or mechanical oscillation method to prepare microbubbles and then freeze-drying to prepare microbubble powder. The destruction of vesicles makes it impossible to produce microbubbles that can meet clinical requirements so far.
At the same time, there is no report about preparing liquid fluorocarbon into gas and using it as a component of ultrasound contrast agent.

Method used

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  • Lipid microvesicle ultrasound angiography powder agent internally containing mixture gas of fluorine carbon/nitrogen gas and production of the same
  • Lipid microvesicle ultrasound angiography powder agent internally containing mixture gas of fluorine carbon/nitrogen gas and production of the same
  • Lipid microvesicle ultrasound angiography powder agent internally containing mixture gas of fluorine carbon/nitrogen gas and production of the same

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Experimental program
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Effect test

Embodiment 1

[0035] Embodiment 1, the preparation of the hollow lipid microbubble powder that contains air

[0036] Reagents: myristoylphosphatidylcholine (DMPC), myristoylphosphatidylethanolamine (DMPE), perfluorohexane (PFH), poloxamer 188, hydroxyethyl starch with a molecular weight of 200kDa, phosphate buffer (pH 7.4) were purchased from Sigma, Germany.

[0037] Equipment: high-speed stirrer, freeze dryer, spray dryer, micro balance.

[0038] Method: Dissolve 0.3g DMPC, 0.02g DMPE and 0.05g poloxamer 188 in 50ml of phosphate buffer, add 21.05ml of perfluorohexane liquid while stirring, and prepare phospholipid microparticles wrapped in perfluorohexane liquid. Bubble. After mixing the phospholipid microbubbles with an equal volume of 10% hydroxyethyl starch phosphate buffer, stir at a constant speed, and use the instantaneous high temperature provided by the spray dryer or freeze-drying method to remove the liquid perfluorohexane in the microbubbles to obtain hollow lipid microvesicl...

Embodiment 2

[0039] Embodiment 2, preparation 2 of hollow lipid microbubble powder containing air

[0040] Reagents: dipalmitoyl-DL-α phosphatidylcholine (DPPC), dipalmitoyl-DL-α phosphatidylethanolamine (DPPE), perfluorohexane (PFH), poloxamer 188, hydroxyl Ethyl starch and phosphate buffer (pH 7.4) were purchased from Sigma, Germany.

[0041] Equipment: high-speed stirrer, freeze dryer, spray dryer, micro balance.

[0042] Method: Dissolve 0.8gDPPC, 0.1gDPPE and 0.1g poloxamer 188 in 50ml phosphate buffer, add 21.05ml perfluorohexane liquid while stirring to prepare phospholipid microbubbles wrapped in perfluorohexane liquid . After mixing the phospholipid microbubbles with an equal volume of 8% hydroxyethyl starch phosphate buffer, stir at a constant speed, and use the instantaneous high temperature provided by the spray dryer or freeze-drying method to remove the liquid perfluorohexane in the microbubbles to obtain hollow lipid microvesicles.

Embodiment 3

[0043] Embodiment 3, preparation of perfluorohexane / nitrogen mixed gas

[0044] Reagents: Perfluorohexane was purchased from Sigma

[0045] Equipment: airtight vials, vacuum plastic bags, catheters

[0046] Method: Put the perfluorohexane liquid in a sealed bottle, one end of the bottle is connected with a vacuum plastic bag, and the other end is connected with the outside world through a glass tube; Introduce nitrogen, and use a vacuum plastic bag to receive the mixed gas of perfluorohexane and nitrogen.

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Abstract

The invention discloses a hollow lipid microfoam composition with fluorocarbon / nitrogen and preparing method, wherein the microfoam filming material is composed of phosphatide, protective and polymer; the phosphatide is selected from phosphatidyl Choline and phosphatidyl ethanolamine; the protective can be middle and macromolecular hydroxyethyl amidon; the polymer is selected from boluoshamu 188 or medically acceptable surface activator for vein injection; the lipid filming material covers the fluorocarbon liquid to form emulsion particle, which forms hollow lipid microball under high temperature instantaneously through gasifying the liquid fluorocarbon; the fluorocarbon / nitrogen is guided to produce the lipid microball for ultrasonic imaging with effectively reinforcing time over 60 min. The invention has high yield rate and fast manufacturing speed, which improves the microball dispersity and microball density effectively.

Description

technical field [0001] The present invention relates to a hollow lipid microbubble composition, more specifically, to a lipid microbubble composition containing a fluorocarbon / nitrogen gas mixture, and the present invention also relates to the composition of the lipid microbubble composition preparation. Background technique [0002] Ultrasound contrast agents are fine spherical particles wrapped in gas, and their shells are composed of proteins, sugars, lipids or polymeric compounds. Ultrasound detection with ultrasound contrast agent is simple, time-consuming, real-time non-invasive, and radiation-free, and has advantages that other inspection methods (such as CT, MRI (magnetic resonance imaging), etc.) cannot match. In human microcirculation and tissue perfusion inspection and imaging, ultrasound contrast agents can significantly improve the detection of lesion tissue in the microcirculation perfusion level, clearly show the blood perfusion characteristics of lesion tiss...

Claims

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Application Information

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IPC IPC(8): A61K49/22
Inventor 王震远
Owner CHONGQING RUNQI PHARMA TECH DEV
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