Composite medicine as well as preparation method and application thereof

A drug and mixed solution technology, which is applied in the direction of drug combination, pharmaceutical formula, anti-infective drugs, etc., can solve the problems of low oral bioavailability, poor water solubility of artesunate, short drug half-life, etc., to achieve rapid blood drug concentration Effects of decline, long survival time, and improvement of resistance

Pending Publication Date: 2021-08-31
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Like most artemisinin drugs, artesunate has poor water solubility, low oral bioavailability, and short drug half-life, among which the half-life of intravenous drugs is as short as 30 minutes
For these problems, existing various dosage forms such as tablet, injection etc. all can't solve this problem.

Method used

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  • Composite medicine as well as preparation method and application thereof
  • Composite medicine as well as preparation method and application thereof
  • Composite medicine as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] In this embodiment, the preparation of packed red blood cells includes the following steps:

[0055] Male SD rats with a body weight of about 200 g were taken, and blood was collected from the retro-orbital venous plexus with a capillary tube with a diameter of 0.5 mm, and the blood volume was 0.2 mL-0.3 mL each time.

[0056] Then centrifuge at 4°C, 3800r / min for 4min, discard the supernatant, remove the plasma and white blood cell layer, add 1mL of pre-cooled PBS to wash once or twice until the supernatant is almost colorless, and the lower layer is packed red blood cells, ready for use. 1 mL of red blood cells contains 10 9 red blood cells.

Embodiment 2

[0058] In this example, the packed erythrocytes prepared in Example 1 were used to prepare a compound drug containing artesunate in erythrocytes without glutaraldehyde modification, and labeled as AS-RBCs, including the following steps:

[0059] (1) Take 0.1 mL of packed erythrocytes prepared in Example 1 and 1 mL of hypotonic solution containing artesunate, mix gently, and incubate at 25° C. for 9 s to obtain erythrocyte mixture. Wherein, the hypotonic solution is formed by dissolving sodium bicarbonate in water, the osmotic pressure of the hypotonic solution is 125mOsm / L, and the concentration of sodium bicarbonate is 0.57wt%; in the hypotonic solution containing artesunate, artesunate The concentration is 4mg / mL.

[0060] (2) Gently mix 1mL of erythrocyte mixture with 0.1mL of hypertonic solution, incubate at 30°C for 20min; The PBS was centrifuged and washed 3 times at 4°C, 3800r / min, 4min / time to obtain the composite drug of artesunate entrapped in erythrocytes without g...

Embodiment 3

[0063] In this example, the packed red blood cells prepared in Example 1 were used to prepare the compound drug of artesunate-loaded red blood cells modified by glutaraldehyde, and labeled as G-AS-RBCs, including the following steps:

[0064] (1) Take 0.1 mL of packed erythrocytes prepared in Example 1 and 1 mL of hypotonic solution containing artesunate, mix gently, and incubate at 25° C. for 9 s to obtain erythrocyte mixture. Wherein, the hypotonic solution is formed by dissolving sodium bicarbonate in water, the osmotic pressure of the hypotonic solution is 125mOsm / L, and the concentration of sodium bicarbonate is 0.57wt%; in the hypotonic solution containing artesunate, artesunate The concentration is 4mg / ml.

[0065] (2) Gently mix 1mL of erythrocyte mixture with 0.1mL of hypertonic solution, incubate at 30°C for 20min; The PBS was centrifuged and washed 3 times at 4°C, 3800r / min, 4min / time, to obtain the drug of artesunate entrapped in erythrocytes without glutaraldehyd...

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Abstract

The invention belongs to the technical field of pharmacy, and particularly relates to a composite medicine and a preparation method and application thereof. The invention relates to a composite medicine, the composite medicine at least comprises red blood cells and artesunate, and the artesunate is entrapped in the red blood cells. Compared with the traditional artesunate injection, the composite medicine disclosed by the invention can realize slow release of the medicine after entering the body, the medicine effect can be maintained for about 9 days, the composite medicine has an obvious slow release effect, and the problems of rapid reduction of the blood concentration of the traditional artesunate injection and side effects caused by short-time multiple administration can be solved, so that malaria can be effectively prevented or treated.

Description

technical field [0001] The invention belongs to the technical field of pharmacy, and in particular relates to a compound medicine and its preparation method and application. Background technique [0002] Artesunate is made by using Chinese unique Artemisia annua as a raw material, extracting the active ingredient artemisinin, and then chemically synthesizing it. It mainly acts on the asexual body of the erythrocytic stage of Plasmodium, which has been discovered so far. The only effective derivative of artemisinin that can be made into water-soluble formulations. Artesunate can kill the plasmodium in the red blood cell stage and achieve antimalarial effect, so it can be used for various malaria patients, especially for the treatment of patients with falciparum malaria and dangerous cerebral malaria resistant to chloroquine and piperaquine. It has the characteristics of high antimalarial activity, rapid fever reduction, short protozoan negative conversion time, and small tox...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K31/357A61K47/54A61K47/69A61K47/46A61P33/06
CPCA61K9/5068A61K9/5089A61K31/357A61K47/54A61K47/6901A61P33/06Y02A50/30
Inventor 邱明丰苏靖徐恩格李怡琛王雪睿张书磊
Owner SHANGHAI JIAO TONG UNIV
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