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Aprepitant micellar sterile freeze-dried preparation for intravenous injection and preparation method thereof

A freeze-dried preparation, aprepitant technology, applied in the field of medicine, can solve the problems of limited clinical use, systemic allergic reactions, low oral bioavailability, etc., and achieve the effects of improving bioavailability and increasing solubility

Active Publication Date: 2022-07-19
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 micellar sterile freeze-dried preparation for intravenous injection and preparation method thereof
  • Aprepitant micellar sterile freeze-dried preparation for intravenous injection and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] In a round-bottomed flask, 75 mg of cultured phosphatidylethanolamine and 15 mg of aprepitant were dissolved in 2 mL of ethanol, and the ethanol was evaporated using a rotary evaporator in a water bath at 50 °C, so that the polymer and the drug formed a A uniform film was then hydrated with 5 mL of deionized water and allowed to stand for 30 min to fully self-assemble to form micelles. An appropriate amount of sodium hydroxide solution was added to adjust the pH to 7.5, and 0.9 g of lactose was added. The filter membrane was filtered and sterilized, and the filtrate was freeze-dried for 72 hours to remove water, and finally a sterile freeze-dried preparation of aprepitant micelle was prepared.

[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%;

[0049] p...

Embodiment 2

[0051] In a round-bottomed flask, 150 mg of cultured phosphatidylethanolamine and 15 mg of aprepitant were dissolved in 3 mL of ethanol, and the ethanol was evaporated using a rotary evaporator in a water bath at 50 °C, so that the polymer and the drug formed a A uniform film was then hydrated with 10 mL of deionized water and allowed to stand for 30 minutes to fully self-assemble to form micelles. An appropriate amount of sodium hydroxide solution was added to adjust the pH to 7.5, and 1.65 g of lactose was added. The filter membrane was filtered and sterilized, and the filtrate was freeze-dried for 72 hours to remove water, and finally a sterile freeze-dried preparation of aprepitant micelle was prepared.

[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 94.5%;

[...

Embodiment 3

[0057] In a round-bottomed flask, 300 mg of cultured phosphatidylethanolamine and 15 mg of aprepitant were dissolved in 5 mL of ethanol, and the ethanol was evaporated using a rotary evaporator in a water bath at 50 °C, so that the polymer and the drug formed a A uniform film was then hydrated with 15 mL of deionized water and allowed to stand for 30 minutes to fully self-assemble to form micelles. An appropriate amount of sodium hydroxide solution was added to adjust the pH to 7.5, and 3.15 g of lactose was added. The filter membrane was filtered and sterilized, and the filtrate was freeze-dried for 72 hours to remove water, and finally a sterile freeze-dried preparation of aprepitant micelle was prepared.

[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 95.3%;

[...

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Abstract

The invention discloses an aseptic freeze-dried preparation of aprepitant micelles for intravenous injection and a preparation method thereof, belonging to the technical field of medicine. The sterile lyophilized preparation of aprepitant micelles for intravenous injection of the present invention comprises aprepitant and methoxy polyethylene glycol derivatized phospholipids, and a pharmaceutically acceptable lyoprotectant. The present invention selects methoxy polyethylene glycol derivatized phospholipid as a solubilizer to increase the solubility of aprepitant and improve bioavailability. At the same time, the aseptic freeze-dried preparation of aprepitant micelles of the present invention does not contain irritating components such as ethanol, nor does it contain Tween-like sensitizing components, thereby improving the safety of clinical use. It is administered by intravenous injection and is convenient for patients with dysphagia and poor oral absorption for the treatment of acute and delayed nausea and vomiting caused by antineoplastic drugs.

Description

technical field [0001] The patent of the present invention relates to a preparation of aprepitant for intravenous injection and a preparation method thereof. The improvement of bioavailability belongs to the field of medical technology. Background technique [0002] Fighting 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 patients' health and treatment effect. According to literature reports, 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.). In addition, some small-molecule targeted drugs are also moderate-intensity emetics, such as imatinib (Journal of Clinical Oncology, 2014.19(3):263-273.). Nausea and vomiting caused by these antineoplas...

Claims

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Application Information

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Patent Type & Authority Patents(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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