Aprepitant micelle sterile freeze-dried preparation for intravenous injection and preparation method of aprepitant micelle sterile freeze-dried preparation

A freeze-dried preparation, aprepitant technology, applied in the field of medicine, can solve the problems of poor gastrointestinal absorption capacity, limited clinical use, and limited use of children

Active Publication Date: 2021-01-05
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the oral capsule inhibits NK-1 receptors in the gastrointestinal tract, it leads to gastrointestinal side effects such as hiccups and constipation (Journal of Clinical Drug Therapy, 2018.16(9):14-28.)
Third, limited clinical use
In addition, most patients with advanced tumors are in a state of cachexia and have poor gastrointestinal absorption capacity, and aprepitant is just a poorly absorbed drug for BCS IV (Int J Pharm, 2004.285(1-2):135-46.), leading to its Poor oral bioavailability
Fourth, the use of children is restricted
Tween excipients are often used as solubilizers for injections, but such excipients are prone to local and systemic allergic reactions (Adv Ther, 2018.35:754–767.)

Method used

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  • Aprepitant micelle sterile freeze-dried preparation for intravenous injection and preparation method of aprepitant micelle sterile freeze-dried preparation
  • Aprepitant micelle sterile freeze-dried preparation for intravenous injection and preparation method of aprepitant micelle sterile freeze-dried preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] In a round-bottomed flask, dissolve 75 mg of cultured phosphatidylethanolamine and 15 mg of aprepitant in 2 mL of ethanol, and use a rotary evaporator to evaporate the ethanol in a water bath at 50 ° C, so that the polymer and the drug form a circle on the wall. Layer a uniform film, then hydrate with 5mL deionized water, let it stand for 30min to fully self-assemble to form micelles, add an appropriate amount of sodium hydroxide solution to adjust the pH value to 7.5, add 0.9g lactose, dissolve and pass through 0.22μm micropores Sterilize by filtration with a membrane filter, freeze-dry the filtrate for 72 hours to remove water, and finally obtain a sterile freeze-dried preparation of aprepitant micelles.

[0046] Determination of relevant properties of aprepitant micellar solution:

[0047] Particle size: determined by dynamic light scattering method, it is 17nm;

[0048] Drug encapsulation efficiency: determined by high performance liquid chromatography, it is 93.8%...

Embodiment 2

[0051] In a round bottom flask, dissolve 150 mg of cultured phosphatidylethanolamine and 15 mg of aprepitant in 3 mL of ethanol, and use a rotary evaporator to evaporate the ethanol in a water bath at 50 ° C, so that the polymer and the drug form a circle on the wall. Layer a uniform film, then hydrate with 10mL deionized water, let it stand for 30min to fully self-assemble to form micelles, add an appropriate amount of sodium hydroxide solution to adjust the pH value to 7.5, add 1.65g of lactose, dissolve and pass through 0.22μm micropores Sterilize by filtration with a membrane filter, freeze-dry the filtrate for 72 hours to remove water, and finally obtain a sterile freeze-dried preparation of aprepitant micelles.

[0052] Determination of relevant properties of aprepitant micellar solution:

[0053] Particle size: determined by dynamic light scattering method, it is 25nm;

[0054] Drug encapsulation efficiency: determined by high performance liquid chromatography, it is 9...

Embodiment 3

[0057] In a round bottom flask, dissolve 300 mg of cultured phosphatidylethanolamine and 15 mg of aprepitant in 5 mL of ethanol, and use a rotary evaporator to evaporate the ethanol in a water bath at 50 ° C, so that the polymer and the drug form a circle on the wall. Layer a uniform film, then hydrate with 15mL deionized water, let it stand for 30min to fully self-assemble to form micelles, add an appropriate amount of sodium hydroxide solution to adjust the pH value to 7.5, add 3.15g of lactose, dissolve and pass through 0.22μm micropores Sterilize by filtration with a membrane filter, freeze-dry the filtrate for 72 hours to remove water, and finally obtain a sterile freeze-dried preparation of aprepitant micelles.

[0058] Determination of relevant properties of aprepitant micellar solution:

[0059] Particle size: determined by dynamic light scattering method, it is 28nm;

[0060] Drug encapsulation efficiency: determined by high performance liquid chromatography, it is 9...

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Abstract

The invention discloses an aprepitant micelle sterile freeze-dried preparation for intravenous injection and a preparation method of the aprepitant micelle sterile freeze-dried preparation, and belongs to the technical field of medicines. The aprepitant micelle sterile freeze-dried preparation for intravenous injection disclosed by the invention comprises aprepitant, methoxy polyethylene glycol derived phospholipid and a pharmaceutically acceptable freeze-drying protective agent. According to the aprepitant micelle sterile freeze-dried preparation disclosed by the invention, the methoxy polyethylene glycol derived phospholipid is selected as a solubilizer, so that the solubility of the aprepitant is increased, and the bioavailability is improved. Besides, the aprepitant micelle sterile freeze-dried preparation disclosed by the invention does not contain irritant components such as ethanol and does not contain sensitizing components such as Tween, so that the clinical use safety is improved. Through intravenous injection administration, the aprepitant micelle sterile freeze-dried preparation is convenient for patients with dysphagia and poor oral absorption to use, and is used for treating acute and delayed nausea and vomiting caused by antitumor drugs.

Description

technical field [0001] The patent of the present invention relates to an aprepitant preparation for intravenous injection and its preparation method. It is composed of aprepitant and methoxypolyethylene glycol derivatized phospholipids, which can improve the solubility of aprepitant and prolong the elimination half-life. The invention improves bioavailability and belongs to the technical field of medicine. Background technique [0002] Fighting against tumors is a comprehensive treatment process, not only to kill cancer cells, but also to improve the patient's cachexia state, enhance physical fitness, pay attention to the patient's spiritual feelings, and compliance with treatment. Nausea and vomiting caused by antineoplastic drugs seriously affect the health of patients and the efficacy of treatment. It has been reported in the literature that more than 75% of chemotherapy drugs are emetogenic, and the incidence of vomiting is as high as 90% (Ann Oncol, 2015.26(6):1081-90....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K9/107A61K47/24A61K31/5377A61P35/00
CPCA61K9/0019A61K9/19A61K9/1075A61K47/24A61K31/5377A61P35/00
Inventor 高钟镐王启明
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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