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Microbubble ultrasound contrast agent containing mitomycin C as well as preparation method and use thereof

An ultrasonic contrast agent, mitomycin technology, which is applied in echo/ultrasonic imaging agents, medical preparations containing active ingredients, and medical preparations without active ingredients, etc., can solve the problems of difficult prodrugs, etc. Improves lipid solubility, improves encapsulation efficiency and drug loading, and has clinically significant effects

Active Publication Date: 2014-09-17
ZHEJIANG PROVINCIAL HOSPITAL OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Synthesis of Mitomycin Oleate and Development of Liposome Preparations, Journal of Fourth Military Medical University 1994, 15 (2) 148, U.S. Patents 7,303,760, 7,276,248, 6,984,396, 6,365,179), but the prodrug is difficult to become a new drug for clinical

Method used

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  • Microbubble ultrasound contrast agent containing mitomycin C as well as preparation method and use thereof
  • Microbubble ultrasound contrast agent containing mitomycin C as well as preparation method and use thereof
  • Microbubble ultrasound contrast agent containing mitomycin C as well as preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036]

[0037] Dissolve lecithin, mitomycin and carbon dichloride in an appropriate amount (about 100 mL), seal, shake at a constant temperature of 35°C for 4 hours, add cholesterol and oleic acid to dissolve, transfer to a rotary evaporator, add lactose, and dry by rotary evaporation. Pack in vials under aseptic conditions, 0.8g per bottle, and then inject sulfur hexafluoride gas to replace the air in the head of the vial, seal it, see figure 1 .

[0038] Inject 0.9% sodium chloride injection 3mL into the vial of mitomycin C microbubble ultrasound contrast agent, then shake the bottle until the microbubbles are uniformly dispersed, absorb a little, dilute 100 times with water, and observe the shape of the microbubbles under a microscope Features, it can be seen that the microbubbles are round, transparent in the middle, thin-walled, uniform in size and stable, see figure 2 . The average diameter of the obtained microbubbles measured by a laser particle size analyzer wa...

Embodiment 2

[0040]

[0041] Dissolve lecithin, mitomycin and an appropriate amount of ethanol (about 100 mL), seal, shake at a constant temperature of 50°C for 6 hours, add vitamin E to dissolve, transfer to a rotary evaporator, add mannose, and dry by rotary evaporation. Under aseptic conditions, it is divided into vials, 0.8g per vial, and then injected with sulfur hexafluoride gas to replace the air in the head of the vial, and then sealed.

Embodiment 3

[0043]

[0044] Dissolve dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, mitomycin and chloroform in an appropriate amount (about 100mL), seal, shake at a constant temperature at 40°C for 6h, add oleic acid to dissolve, transfer to a rotary evaporator, add Sorbitol, dried by rotary evaporation. It is divided into vials under sterile conditions, 0.8g per vial, and then injected with perfluoropropane gas to replace the air in the head of the vial, and then sealed.

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Abstract

The invention discloses a preparation method of a microbubble ultrasound contrast agent containing mitomycin C. The preparation method is characterized in that a phospholipid complex is prepared by use of the phospholipid and the mitomycin C so that the fat solubility of the mitomycin is greatly improved, and then the phospholipid complex is prepared into a lipidosome so that the encapsulation efficiency and the drug-loading capacity of the mitomycin C lipidosome are improved. The obtained lipidosome is freeze-dried by use of a freeze-drying protecting agent and filled with a gas to obtain the microbubble ultrasound contrast agent containing the mitomycin C. Before use, normal saline is added to the microbubble ultrasound contrast agent by a demand quantity, and then the microbubble ultrasound contrast agent can be used after being oscillated and hydrated. The obtained drug-loading ultrasonic microbubbles are capable of realizing real-time detection and diagnosis on the generation and development of tumors and curative effects by virtue of ultrasonic imaging; and besides, the purpose of controlled targeted drug release can be achieved by virtue of passive targeting of microbubbles and by releasing the drug by ultrasonically crushing the microbubbles. As a result, the microbubble ultrasound contrast agent has great significance for preventing, diagnosing and treating tumors.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a drug-loaded microbubble ultrasonic contrast agent. Background technique [0002] Ultrasound medicine not only develops rapidly in the traditional diagnostic field, but also gradually extends to the therapeutic field. Microbubble ultrasound contrast agent can also be used as a new type of drug carrier while being used as a diagnostic tool. It can not only enhance ultrasound imaging, but also be used as a carrier for targeted drug delivery. Microbubble ultrasound contrast agent is a kind of microbubble with a fixed gas shell, which greatly enhances the backscattering of ultrasound, thereby enhancing the co-wave signal of blood flow and the Doppler signal of blood flow in blood vessels. Ultrasound contrast agent has been Commonly used in ultrasound diagnosis. The film material constituting the microbubble ultrasound contrast agent is a good carrier of drugs, which can ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22A61K9/127A61K47/48A61K31/407A61P35/00A61K47/69
Inventor 梁哲浩孙华琴孙泉袁帅郭家宝董蓓莉王华俞振伟梁漪梁文权
Owner ZHEJIANG PROVINCIAL HOSPITAL OF TRADITIONAL CHINESE MEDICINE
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