WO2022065860A1 - Préparation pouvant être inhalée comprenant du nafamostat ou du camostat - Google Patents

Préparation pouvant être inhalée comprenant du nafamostat ou du camostat Download PDF

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Publication number
WO2022065860A1
WO2022065860A1 PCT/KR2021/012923 KR2021012923W WO2022065860A1 WO 2022065860 A1 WO2022065860 A1 WO 2022065860A1 KR 2021012923 W KR2021012923 W KR 2021012923W WO 2022065860 A1 WO2022065860 A1 WO 2022065860A1
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WO
WIPO (PCT)
Prior art keywords
inhalation
formulation
nafamostat
camostat
salt
Prior art date
Application number
PCT/KR2021/012923
Other languages
English (en)
Korean (ko)
Inventor
박일영
박천웅
강지현
Original Assignee
충북대학교 산학협력단
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
Priority claimed from KR1020210123627A external-priority patent/KR102664833B1/ko
Application filed by 충북대학교 산학협력단 filed Critical 충북대학교 산학협력단
Publication of WO2022065860A1 publication Critical patent/WO2022065860A1/fr

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    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • 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

Definitions

  • Nafamostat was synthesized in the 1990s (Nakayama et al. Synthesis and Structure-Activity Study of Protease Inhibitors. V. Chemical Modification of 6-Amidino-2-naphthyl 4-Guanidinobenzoate. Chem. Pharm. Bull. (1993) 41(1):117) It is a serine protease inhibitor and relieves symptoms of acute pancreatitis and when using an extracorporeal dialysis machine and extracorporeal membrane oxygenation (ECMO) in dialysis patients It has been approved and used in Korea and Japan as an injection for the purpose of preventing blood clotting.
  • ECMO extracorporeal membrane oxygenation
  • Napamostat's short half-life and difficult passage through biological membranes make it an advantage as an injection for the purpose of preventing blood coagulation in an extracorporeal dialysis machine for dialysis patients, but it is a serious disadvantage as a treatment for COVID-19.
  • the cells in the oral cavity, nasal cavity, trachea, and lung cavity are located at the location where the virus proliferates and destroys cells by primary invasion and re-invades into other cells.
  • Napamostat has to reach the side that comes into contact with the air, the outer surface of the cell where TMPRSS2, which is the point of action of napamostat, is present). In addition, it effectively avoids esterases present in lung tissue (D.
  • nafamostat mesylate 25 mg/mL, lecithin 25 mg/mL, and lipophilic solution containing 0.5% mannitol A sterile formulation was prepared. Mannitol plays a role of complementing osmotic pressure, and lecithin plays a role in inhibiting hydrolysis of nafamostat by competitively binding to esterases present in the respiratory lumen.
  • nafamostat mesylate 25 mg/mL and 0.5% mannitol containing 0.5% mannitol was prepared.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • Inorganic Chemistry (AREA)
  • Biophysics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Emergency Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une préparation pouvant être inhalée comprenant du nafamostat, du camostat ou leurs sels. La préparation pouvant être inhalée peut être inhalée à travers le nez et est ainsi excellente pour prévenir ou traiter une infection nasale primaire par un virus, se présente sous une forme simple qui peut facilement être auto-administrée par un patient et peut être appliquée à un patient ayant une maladie avancée par l'intermédiaire d'un respirateur. Par conséquent, la présente invention peut être utilisée dans la technologie de prévention ou de traitement des maladies liées au coronavirus ou au virus de la grippe. La préparation pouvant être inhalée administre également un médicament à l'aide d'une inhalation contrairement au procédé d'administration par voie orale ou par injection existant, et comprend de plus un substrat qui fonctionne de manière compétitive sur l'estérase et les sels qui retardent l'élution, et inhibe ainsi in vivo la dégradation du nafamostat ou du camostat pour maintenir une bonne quantité de résidu dans les parties appliquées.
PCT/KR2021/012923 2020-09-24 2021-09-23 Préparation pouvant être inhalée comprenant du nafamostat ou du camostat WO2022065860A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2020-0124178 2020-09-24
KR20200124178 2020-09-24
KR1020210123627A KR102664833B1 (ko) 2020-09-24 2021-09-16 나파모스타트 또는 카모스타트를 포함하는 흡입용 제제
KR10-2021-0123627 2021-09-16

Publications (1)

Publication Number Publication Date
WO2022065860A1 true WO2022065860A1 (fr) 2022-03-31

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2021/012923 WO2022065860A1 (fr) 2020-09-24 2021-09-23 Préparation pouvant être inhalée comprenant du nafamostat ou du camostat

Country Status (1)

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WO (1) WO2022065860A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993019771A1 (fr) * 1992-03-27 1993-10-14 Kirin Brewery Company, Limited Preparation administrable par voie nasale contenant un facteur de stimulation de colonies granulocytaires
US20030060451A1 (en) * 2001-05-29 2003-03-27 Rajneesh Taneja Enhancement of oral bioavailability of non-emulsified formulations of prodrug esters with lecithin
KR20060040754A (ko) * 2000-07-04 2006-05-10 파마겐 래보레토리즈 리미티드 낭포성 섬유증(ｃｆ) 및 만성 폐색성 폐병(ｃｏｐｄ)의치료에 사용되는 세크레틴 수용체 리간드의 용도
KR20070118257A (ko) * 2005-04-14 2007-12-14 노파르티스 아게 유기 화합물

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993019771A1 (fr) * 1992-03-27 1993-10-14 Kirin Brewery Company, Limited Preparation administrable par voie nasale contenant un facteur de stimulation de colonies granulocytaires
KR20060040754A (ko) * 2000-07-04 2006-05-10 파마겐 래보레토리즈 리미티드 낭포성 섬유증(ｃｆ) 및 만성 폐색성 폐병(ｃｏｐｄ)의치료에 사용되는 세크레틴 수용체 리간드의 용도
US20030060451A1 (en) * 2001-05-29 2003-03-27 Rajneesh Taneja Enhancement of oral bioavailability of non-emulsified formulations of prodrug esters with lecithin
KR20070118257A (ko) * 2005-04-14 2007-12-14 노파르티스 아게 유기 화합물

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KIRKPATRICK D. LYNN, MILLARD JEFFREY: "Evaluation of nafamostat mesylate safety and inhibition of SARS-CoV-2 replication using a 3-dimensional human airway epithelia model", BIORXIV, 16 September 2020 (2020-09-16), XP055913520, Retrieved from the Internet <URL:https://www.biorxiv.org/content/10.1101/2020.09.16.300483v1.full.pdf> DOI: 10.1101/2020.09.16.300483 *

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