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Quick-release preparation for targeted treatment of heart failure

An immediate-release preparation and a technology for heart failure, applied in the field of nitric oxide preparations, can solve the problems that cannot be directly made into ordinary pharmaceutical preparations, target delivery therapy has not yet been seen, and achieve convenient storage and transportation, good affinity Sex and biocompatibility, the effect of precise targeting

Active Publication Date: 2020-11-24
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, nitric oxide molecules are in gaseous form, and nitric oxide gas (NO) is slightly soluble in water, and its solubility in water at 20°C is only 5.6×10-3g / L (equivalent to 0.186μmol / L), unable to be directly made into common pharmaceutical preparations
[0006] Therefore, although nitric oxide has a good therapeutic potential for heart failure, nitric oxide is used as a gas, and there are no research reports on how to efficiently carry nitric oxide gas in pharmaceutical preparations for targeted delivery therapy.

Method used

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  • Quick-release preparation for targeted treatment of heart failure

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Experimental program
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Effect test

Embodiment 1

[0022] The preparation of the immediate-release preparation of embodiment 1 heart failure targeted therapy

[0023] According to the component ratio of Table 1, prepare the immediate-release preparation for ultrasonic diagnosis and treatment of heart failure of the experimental group, specifically including the following steps:

[0024] (1) Take hydrogenated soybean lecithin and heparin-poloxamer with a mass ratio of 1:2, add 10 times the mass of water for injection, heat to 65°C, mix well, transfer to an insulated and pressure-resistant container with a stopper, and vacuumize Then inject nitric oxide gas, shake at high speed for 3 minutes through a vortex mixer, and carry out particle size homogenization treatment through a sieve with a specified aperture under high pressure. After the temperature drops to 15°C, add basic fibrils with the same molar mass as heparin-poloxamer Cytokines are mixed evenly to obtain drug-loaded microbubbles.

[0025] (2) Take poloxamer and hydrox...

Embodiment 2

[0031] Application effect of the immediate-release preparation of embodiment 2 heart failure targeted therapy

[0032] (1) Establishment of heart failure model animals

[0033] Japanese big-eared white rabbits, weighing 1.5-2.5kg, aged 3-4 months, injected adriamycin through the rabbit ear vein, 1mg / kg each time, twice a week, for 8 weeks in total, the total amount was about equivalent to 320mg / m 2 , doxorubicin was diluted to 1 mg / mL with saline. Heart failure model animals were tested by echocardiography to determine whether the modeling was successful.

[0034] (2) Evaluation of the therapeutic effect of each group of immediate-release preparations

[0035] The Japanese big-eared white rabbits with successful modeling of heart failure were selected and divided into several groups according to the design in Table 1, and the drug administration experiment was carried out on the first, third, and fifth days. Position the probe on the heart, and inject 0.5mL of each group o...

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Abstract

The invention provides a quick-release preparation for targeted treatment of a heart failure. The quick-release preparation is composed of a basic solution and drug-loaded microbubbles, wherein the basic solution comprises the following components: poloxamer and hydroxyethyl starch; the mass ratio of the poloxamer to the hydroxyethyl starch is 1: 10; the drug-loaded microbubbles are composed of nitric oxide microbubbles carrying basic fibroblast growth factors; the nitric oxide microbubbles are vesicles formed by wrapping nitric oxide gas with hydrogenated soyabean lecithin and heparin-poloxamer as bubble film materials; the mass ratio of the hydrogenated soyabean lecithin to the heparin-poloxamer is 1: 2; the molar mass of the basic fibroblast growth factors is equal to the molar mass ofthe heparin-poloxamer; the basic fibroblast growth factor is adhered to the surfaces of the nitric oxide microbubbles; the particle size range of the drug-loaded microbubbles is 2-5 microns; and the concentration of the drug-loaded microbubbles is 6 * 10<6>-9 * 10<6> / mL. According to the invention, after intravenous injection of the quick-release preparation for targeted treatment of the heart failure, accurate positioning and targeted delivery of a heart part are realized through an ultrasonic mediation technology, and the quick-release preparation is used for treatment of the heart failure.

Description

technical field [0001] The invention relates to a nitric oxide preparation, in particular to an immediate release preparation for targeted therapy of heart failure. Background technique [0002] Heart failure is a complex clinical syndrome, which is the pathophysiology of abnormal heart structure and function caused by various reasons, which lead to the heart pumping unable to meet the metabolic needs of the tissue, or the heart can only pump blood normally under the condition of elevated ventricular filling pressure The state, including rapid onset or slowly progressive cardiac dysfunction, has high long-term cardiac mortality, cardiovascular events, and rehospitalization rates, and poor quality of life for patients. Once heart failure is diagnosed, about half of patients die within 5 years, and the 1-year mortality rate of severe patients is as high as 50%. [0003] Studies have found that nitric oxide can regulate normal cardiovascular activity and plays a significant ro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/00A61K9/00A61K47/10A61K47/36A61K47/42A61K47/24A61P9/04A61K49/22
CPCA61K33/00A61K9/0087A61K47/10A61K47/36A61K47/42A61K47/24A61P9/04A61K49/223
Inventor 赵应征鲁翠涛陈斌王丽芬罗兰子陈杭波
Owner WENZHOU MEDICAL UNIV
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