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WO2015027848A1 - Méthode pour administrer une formulation comportant du peramivir et/ou un dérivé correspondant - Google Patents

Méthode pour administrer une formulation comportant du peramivir et/ou un dérivé correspondant Download PDF

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Publication number
WO2015027848A1
WO2015027848A1 PCT/CN2014/084836 CN2014084836W WO2015027848A1 WO 2015027848 A1 WO2015027848 A1 WO 2015027848A1 CN 2014084836 W CN2014084836 W CN 2014084836W WO 2015027848 A1 WO2015027848 A1 WO 2015027848A1
Authority
WO
WIPO (PCT)
Prior art keywords
administration
peramivir
derivatives
administration method
inhalation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2014/084836
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English (en)
Chinese (zh)
Inventor
陈永奇
白仲虎
丁玉龙
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO2015027848A1 publication Critical patent/WO2015027848A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses

Definitions

  • the invention belongs to the field of pharmaceutical preparations, in particular to (1S, 2S, 3S, 4R)-3-[(lS)-l-acetylamino-2-ethyl-butyl]-4-mercapto-2-hydroxy-cyclo Amyl-1-carboxylic acid (C 15 H 28 N 4 0 4 : peramivir) and derivatives thereof such as pharmaceutically acceptable salts, esters, hydrates or amorphous compounds as neuraminidase inhibitors, A method for treating influenza by direct respiratory administration through a lung target.
  • Influenza is an acute respiratory infection caused by influenza virus. It is highly contagious, has a high incidence, and is prone to outbreaks or pandemics.
  • Hemagglutinin and neuraminidase are two large glycoproteins outside the viral particle. Hemagglutinin is a lectin-mediated viral binding to a target cell and allows the viral genome to enter the target cell, while neuraminidase It involves the release of progeny virus from infected cells by cleavage of mature viral particles bound to sugars. Therefore, these proteins are the targets of antiviral drugs, and they are also antigens that cause antibodies. For example, influenza A virus can be divided into different serotypes according to the response of antibodies to HA and NA, such as H1N1, H2N2, H3N2, etc. The popular one is H7N9.
  • RNA polymerase Since RNA polymerase does not have a proofreading function, an RNA polymerase that relies on the RNA replication viral genome causes an error of approximately every 10,000 bases, which is approximately the length of the influenza virus RNA. Therefore, most newly generated influenza viruses are mutants that cause antigenic drift, and the antigen slowly changes over the surface of the virus over time. If more than one virus simultaneously infects one cell, the genomic separation of the eight isolated fragments on the viral RNA allows for the mixing or recombination of multiple viral RNAs. This produces rapid antigenic changes in the genetic changes caused by the virus, forming a sudden shift from one antigen to another. This sudden and large change causes the virus to infect new host species and quickly overcome protective immunity, becoming a highly pathogenic virus.
  • Neuraminidase is a glycoside hydrolase that cleaves the glycosidic bond of neuraminidase, catalyzes the hydrolysis of sialic acid, assists in the mobility of mucus virus particles through the respiratory tract and the release of host cells from influenza virus. Dye new cells. Because of the relatively deep activation sites, low molecular weight inhibitors can have a number of favorable interactions and accessible methods to competitively occupy the site of neuraminidase, thereby inhibiting viral flow and progeny virus detachment. If the activity of neuraminidase is blocked, the newly produced virus
  • Peramivir C 15 H 28 N 4 0 4 (IS , 2S, 3S, 4R)-3-[(lS)-l-acetylamino-2-ethyl-indenyl]-4-indolyl-2 -Hydroxy-cyclopentyl-1-carboxylic acid is a compound with some sort of oseltamivir, zanamivir structure, Johnson and Johnson have been developed as oral drugs, but due to poor bioavailability BioCryst is now being developed as an intravenous dosage form with an intravenous infusion of 300 or 600 mg ⁇ 30 minutes. The US FDA in 2009 authorized the emergency use of patients with suspected H1N1 infections in hospitals.
  • the peramivir and/or its derivative according to the present invention means a compound such as peramivir and/or a physiologically acceptable pharmaceutically acceptable salt, or ester, hydrate or amorphous substance thereof.
  • a method of administration comprising a formulation of peramivir and/or a derivative thereof, said administration being carried out by inhalation.
  • the present invention proposes that the treatment of respiratory diseases should be carried out by inhalation administration, so that the target can be directly administered to the lungs directly.
  • the target here refers to a partially infected cell in the lung where the influenza virus is located or the virus itself in the lungs.
  • the flu virus is characterized by the passage of the respiratory tract into the lungs of the human body, with the help of hemagglutinin on the surface of the virus.
  • HA hemagglutinin
  • the neuraminidase (NA) on the surface of the virus acts on the receptor of the nuclear protein, binds the nucleoprotein of the virus and the epithelial cells, forms an RNA-type soluble antigen in the nucleus, and exudes to the periphery of the cytoplasm, and copies the progeny.
  • the virus through the action of neuraminidase, excretes epithelial cells in a budding manner.
  • the period of a replication process is 4 to 6 hours, and the discharged virus spreads to nearby cells, which are exhaled by the respiratory tract and spread the virus particles through the air. Therefore, the virus is mainly confined to the respiratory tract, and there is little evidence that the highly pathogenic virus replicates in other organs.
  • the traditional mode of administration such as oral administration, must be absorbed into the bloodstream, enter the blood circulation, and then metabolized by the enzymes in the liver to become active substances, and then reach the lungs of the virus where it is located through the systemic blood circulation.
  • the intravenous injection method has less steps of intestinal absorption, the other steps and oral administration require enzymatic hydrolysis and then blood circulation to the lungs.
  • the present invention selects the direct pulmonary administration of peramivir and/or its derivative by respiratory inhalation, and delivers the active antiviral drug directly to the place where the respiratory target virus gathers, and the drug quickly reaches the infected area to be localized.
  • High concentrations occupy the site of viral neuraminidase, making it impossible for the virus to move and progeny to regenerate and spread, so as to improve the efficiency of treatment and reduce side effects should be the ideal choice.
  • each compound is administered as a pharmaceutical preparation component by inhalation.
  • Micronization can be prepared by any of the techniques well known in the art of pharmacy, such as jet milling, spray drying, spray freeze drying, supercritical fluids.
  • the present invention further provides a pharmaceutical preparation for treating a cold caused by influenza virus on the basis of 2-6 times, preferably 3 times to 4 times per day, the pharmaceutical preparation comprising peramivir or its physiologically acceptable a salt, an ester, a hydrate, or an amorphous substance, and a pharmaceutically acceptable carrier or excipient or adjuvant.
  • the pharmaceutical preparation herein means a form suitable for administration by inhalation.
  • the permeation method of the peramivir and/or its derivative has a maximum particle diameter of not more than 50 ⁇ m, for example, 2 ⁇ m, 4 ⁇ m, 7 ⁇ m, 11 ⁇ m, 15 ⁇ m, 19 ⁇ m, 22 ⁇ m, and 26 ⁇ , 29 ⁇ , 33 ⁇ , 38 ⁇ , 42 ⁇ , 46 ⁇ , 49 ⁇ , etc., preferably not more than 20 ⁇ , further preferably 1-10 ⁇ , particularly preferably 1-5 ⁇ .
  • the active ingredient has a maximum particle size of less than 50 ⁇ , preferably less than 20 ⁇ , preferably in the range of 1-10 ⁇ , more preferably 1-5 ⁇ .
  • Example 3 Inhalation of a 5 mg peramivir metered dose inhaler

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Otolaryngology (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une méthode pour administrer une formulation comportant du péramivir et/ou un dérivé correspondant ; cette méthode permettant de traiter des refroidissements causés par un virus de la grippe ; et l'administration se faisant par l'intermédiaire de plus d'un ou de deux éléments parmi les éléments suivants : poudre sèche, insufflateur de poudre, inhalateur à doses quantifiées ou nébuliseur.
PCT/CN2014/084836 2013-08-26 2014-08-20 Méthode pour administrer une formulation comportant du peramivir et/ou un dérivé correspondant Ceased WO2015027848A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2013103766268A CN103446051A (zh) 2013-08-26 2013-08-26 含有帕拉米韦和/或其衍生物制剂的给药方法
CN201310376626.8 2013-08-26

Publications (1)

Publication Number Publication Date
WO2015027848A1 true WO2015027848A1 (fr) 2015-03-05

Family

ID=49729173

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2014/084836 Ceased WO2015027848A1 (fr) 2013-08-26 2014-08-20 Méthode pour administrer une formulation comportant du peramivir et/ou un dérivé correspondant

Country Status (2)

Country Link
CN (1) CN103446051A (fr)
WO (1) WO2015027848A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3932400A4 (fr) * 2019-02-25 2022-09-21 Guangzhou Nanxin Pharmaceutical Co., Ltd. Inhalant de type solution de péramivir et son procédé de préparation

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106420621A (zh) * 2016-10-09 2017-02-22 默栢瑞成都生物技术有限公司 帕拉米韦粉剂的制备方法
CN111067879B (zh) * 2020-01-20 2022-08-09 珠海瑞思普利医药科技有限公司 一种抗肿瘤组合物吸入粉雾剂及其制备方法
CN111265499B (zh) * 2020-02-17 2022-11-15 江苏艾立康医药科技有限公司 一种洛匹那韦吸入气雾剂及其制备方法
CN113491678B (zh) * 2020-04-07 2023-01-20 知和(山东)大药厂有限公司 一种盐酸阿比朵尔吸入剂及其制备方法
CN111358773B (zh) * 2020-04-10 2021-03-30 广州南鑫药业有限公司 一种帕拉米韦干粉吸入剂及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009143011A1 (fr) * 2008-05-20 2009-11-26 Novartis Ag Compositions antivirales, procédés de fabrication et d’utilisation de ces compositions, et système de délivrance pulmonaire de ces compositions
WO2011035128A1 (fr) * 2009-09-17 2011-03-24 Mutual Pharmaceutical Company, Inc. Procédé de traitement de l'asthme avec des agents antiviraux

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009143011A1 (fr) * 2008-05-20 2009-11-26 Novartis Ag Compositions antivirales, procédés de fabrication et d’utilisation de ces compositions, et système de délivrance pulmonaire de ces compositions
WO2011035128A1 (fr) * 2009-09-17 2011-03-24 Mutual Pharmaceutical Company, Inc. Procédé de traitement de l'asthme avec des agents antiviraux

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3932400A4 (fr) * 2019-02-25 2022-09-21 Guangzhou Nanxin Pharmaceutical Co., Ltd. Inhalant de type solution de péramivir et son procédé de préparation

Also Published As

Publication number Publication date
CN103446051A (zh) 2013-12-18

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