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Preparation method of a diagnosis and treatment preparation integrating ultrasound contrast-enhanced imaging and hyperthermia

A contrast-enhanced ultrasound and integrated technology, applied in the field of biomedical materials, can solve the problems of difficult diagnosis and treatment of extravascular diseases, limit the application of indocyanine green, and short cycle time, and achieve excellent biocompatibility and degradability, The effect of prolonging the blood circulation time and the simple preparation method

Inactive Publication Date: 2019-02-05
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although micron-scale ultrasound contrast agents represented by SonoVue have been successfully applied to varying degrees, there are still many problems: on the one hand, the particle size is large, so it is only limited to the development of the blood pool, and it is not easy to realize the contrast agent outside the blood vessel. Diagnosis and treatment of diseases; on the other hand, because the capsule material of Sonovo is lipid, the lipid properties are not stable enough, the duration in the body is not long enough, and the duration of contrast is short, so it is necessary to use microbubble contrast agent to achieve tumor detection. Molecular imaging still has certain difficulties
However, free indocyanine green is easy to aggregate rapidly in polar solvents, and its stability is poor. It is easy to be quickly cleared in plasma and has a short circulation time in the body. These defects greatly limit the application of indocyanine green.

Method used

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  • Preparation method of a diagnosis and treatment preparation integrating ultrasound contrast-enhanced imaging and hyperthermia
  • Preparation method of a diagnosis and treatment preparation integrating ultrasound contrast-enhanced imaging and hyperthermia
  • Preparation method of a diagnosis and treatment preparation integrating ultrasound contrast-enhanced imaging and hyperthermia

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Weigh 1 mg of organic-inorganic composite lipid and 0.1 mg of polyethylene glycol (DSPE-PEG2000) into 0.1 mL of absolute ethanol to disperse. Take 1 mg of menthol powder and add it to a serum bottle filled with 1 mL of ultrapure water, heat it in a water bath to 45 °C, and then add 1 mL of an aqueous solution with a concentration of 1 mg / mL indocyanine green. Under the ultrasonic condition of a water bath, the ethanol solution of organic-inorganic composite lipid and polyethylene glycol obtained above is quickly injected into the mixed solution of indocyanine green, menthol and water to obtain a pre-emulsion. After the pre-emulsion was ultrasonicated with the probe of an ultrasonic cell disruptor for 0.5 min (set the ultrasonic power to 30w, work for 3s, stop for 3s), a silicone lipid nanoemulsion loaded with indocyanine green and menthol was obtained. Finally, the free indocyanine green is removed by dialysis, and the organic-inorganic composite lipid containing indocy...

Embodiment 2

[0035] Weigh 50mg of organic-inorganic composite lipid and 10mg of polyethylene glycol (DSPE-PEG2000) into 1mL of absolute ethanol to disperse. Take 25 mg of menthol powder and add it to a serum bottle filled with 20 mL of ultrapure water, heat it in a water bath to 45 ° C, and then add 10 mL of an aqueous solution with a concentration of 1 mg / mL indocyanine green. Under the ultrasonic condition of a water bath, the ethanol solution of organic-inorganic composite lipid and polyethylene glycol obtained above is quickly injected into the mixed solution of indocyanine green, menthol and water to obtain a pre-emulsion. After the pre-emulsion was ultrasonicated with the probe of an ultrasonic cell disruptor for 5 minutes (set the ultrasonic power to 30w, work for 3s, and stop for 3s), a silicon lipid nanoemulsion loaded with indocyanine green and menthol was obtained. Finally, the free indocyanine green is removed by dialysis, and the organic-inorganic composite lipid containing in...

Embodiment 3

[0037]Weigh 25mg of organic-inorganic composite lipid and 5mg of polyethylene glycol (DSPE-PEG2000) into 5mL of absolute ethanol to disperse. Take 12 mg of menthol powder and add it to a serum bottle filled with 10 mL of ultrapure water, heat it in a water bath to 45 ° C, and then add 5 mL of an aqueous solution with a concentration of 1 mg / mL indocyanine green. Under the ultrasonic condition of a water bath, the ethanol solution of organic-inorganic composite lipid and polyethylene glycol obtained above is quickly injected into the mixed solution of indocyanine green, menthol and water to obtain a pre-emulsion. After the pre-emulsion was ultrasonicated with the probe of an ultrasonic cell disruptor for 2 minutes (set the ultrasonic power to 30w, work for 3s, and stop for 3s), a silicone lipid nanoemulsion loaded with indocyanine green and menthol was obtained. Finally, the free indocyanine green is removed by dialysis, and the organic-inorganic composite lipid containing indo...

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Abstract

The invention relates to a preparation method of a diagnosis and treatment preparation integrating ultrasound contrast and thermal therapy. The preparation method comprises the following steps: (1) dissolving 1-50 mg of organic-inorganic complex lipid and 0.1-10 mg of polyethylene glycol into 0.1-1 mL of absolute ethyl alcohol; (2) dissolving 1-25 mg of menthol into 1-20 mL of ultrapure water, carrying out water-bath heating till the temperature reaches 45 DEG C, mixing the obtained solution with 1-10 mL of an aqueous solution of indocyanine green; (3) rapidly injecting the ethanol solution of the organic-inorganic complex lipid and polyethylene glycol obtained in the step (1) into the mixed solution obtained in the step (2) under the water bath and ultrasonic wave conditions; and (4) carrying out probe ultrasound treatment, thus obtaining organic-inorganic complex lipid nano-particles, wherein the inner cavities of the organic-inorganic complex lipid nano-particles are loaded with the indocyanine green and menthol and the surfaces of the organic-inorganic complex lipid nano-particles are covered by inorganic silicate shells being in nanoscale thickness and having good biocompatibility. The complex lipid diagnosis and treatment preparation provided by the invention can realize the photothermal therapy on tumor tissues under the ultrasound visual observation, the stability is good, no obvious toxic and side effects are caused to the human body, in addition, the preparation method is simple, and the requirements on devices are low.

Description

technical field [0001] The invention relates to the field of biomedical materials, in particular to a method for preparing a diagnosis and treatment preparation integrating ultrasound contrast-enhanced imaging and hyperthermia. Background technique [0002] Cancer is a highly heterogeneous and highly adaptable disease, and it is necessary to choose different types of diagnosis and treatment options according to the characteristics of the patient and the progress of the disease. A class of nano-therapeutic preparations that integrate diagnostic and therapeutic functions has gradually emerged in the field of tumor treatment. The combination of nano-preparations in diagnosis and treatment can provide patients with a variety of personalized diagnosis and treatment options, thereby improving the treatment effect. Therefore, it is of great significance to develop new multifunctional nano-diagnosis and treatment preparations. Ultrasound imaging is a widely used diagnostic method i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K41/00A61K9/51A61K47/04A61K47/10A61P35/00
CPCA61K9/5115A61K9/5146A61K41/0052A61K49/221A61K49/223
Inventor 曹众王春安蒋庆
Owner SUN YAT SEN UNIV
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