ZA201004654B - Phenylephrine pharmaceutical formulations and compositions for transmucosal absorption - Google Patents

Phenylephrine pharmaceutical formulations and compositions for transmucosal absorption

Info

Publication number
ZA201004654B
ZA201004654B ZA2010/04654A ZA201004654A ZA201004654B ZA 201004654 B ZA201004654 B ZA 201004654B ZA 2010/04654 A ZA2010/04654 A ZA 2010/04654A ZA 201004654 A ZA201004654 A ZA 201004654A ZA 201004654 B ZA201004654 B ZA 201004654B
Authority
ZA
South Africa
Prior art keywords
compositions
pharmaceutical formulations
transmucosal absorption
phenylephrine
phenylephrine pharmaceutical
Prior art date
Application number
ZA2010/04654A
Other languages
English (en)
Inventor
Mohammed A Kabir
Xiaoming Chen
Dennis Nelson
John O'mullane
David Monteith
Joseph P Reo
Jiansheng Wan
Original Assignee
Schering-Plough Healthcare Products Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40510498&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ZA201004654(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Schering-Plough Healthcare Products Inc filed Critical Schering-Plough Healthcare Products Inc
Publication of ZA201004654B publication Critical patent/ZA201004654B/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A61K9/0058Chewing gums
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2013Organic compounds, e.g. phospholipids, fats
    • A61K9/2018Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2027Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4866Organic macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Emergency Medicine (AREA)
  • Immunology (AREA)
  • Otolaryngology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
ZA2010/04654A 2007-12-07 2010-07-01 Phenylephrine pharmaceutical formulations and compositions for transmucosal absorption ZA201004654B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US1222307P 2007-12-07 2007-12-07
PCT/US2008/085523 WO2009076165A1 (en) 2007-12-07 2008-12-04 Phenylephrine pharmaceutical formulations and compositions for transmucosal absorption

Publications (1)

Publication Number Publication Date
ZA201004654B true ZA201004654B (en) 2011-03-30

Family

ID=40510498

Family Applications (1)

Application Number Title Priority Date Filing Date
ZA2010/04654A ZA201004654B (en) 2007-12-07 2010-07-01 Phenylephrine pharmaceutical formulations and compositions for transmucosal absorption

Country Status (17)

Country Link
US (1) US20090280160A1 (enExample)
EP (1) EP2237767A1 (enExample)
JP (1) JP2011506337A (enExample)
KR (1) KR20100102632A (enExample)
CN (1) CN101938991A (enExample)
AR (1) AR069572A1 (enExample)
AU (1) AU2008335464A1 (enExample)
BR (1) BRPI0820673A2 (enExample)
CA (1) CA2709208A1 (enExample)
CL (1) CL2008003615A1 (enExample)
CO (1) CO6321221A2 (enExample)
MX (1) MX2010006284A (enExample)
PE (1) PE20091084A1 (enExample)
RU (1) RU2010127737A (enExample)
TW (1) TW200932208A (enExample)
WO (1) WO2009076165A1 (enExample)
ZA (1) ZA201004654B (enExample)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2795291T3 (es) 2013-02-13 2020-11-23 Procter & Gamble Medicamento con sabor a anís
US20190008759A1 (en) * 2014-07-03 2019-01-10 Darren Rubin Safer and more effective methods of transmucosal delivery for raising blood pressure and stimulating the body
MA41689A (fr) * 2014-10-15 2017-08-22 Bioxcel Corp Prévention ou traitement de troubles du sommeil au moyen d'une formulation de dexmédétomidine
US12427121B2 (en) 2016-05-05 2025-09-30 Aquestive Therapeutics, Inc. Enhanced delivery epinephrine compositions
US11273131B2 (en) 2016-05-05 2022-03-15 Aquestive Therapeutics, Inc. Pharmaceutical compositions with enhanced permeation
US12433850B2 (en) 2016-05-05 2025-10-07 Aquestive Therapeutics, Inc. Enhanced delivery epinephrine and prodrug compositions
JP7653218B2 (ja) * 2016-05-05 2025-03-28 アクエスティブ セラピューティクス インコーポレイテッド 送達増強エピネフリン組成物
ES2980126T3 (es) 2016-12-31 2024-09-30 Bioxcel Therapeutics Inc Uso de dexmedetomidina para el tratamiento de la agitación
WO2018130603A1 (en) 2017-01-11 2018-07-19 Ferring B.V. A fast disintegrating pharmaceutical composition
WO2019021476A1 (ja) * 2017-07-28 2019-01-31 社会医療法人蘇西厚生会 まつなみリサーチパーク アレルギー症状の予防又は治療剤
JP2020535162A (ja) * 2017-09-27 2020-12-03 アクエスティブ セラピューティクス インコーポレイテッド 増強された送達のエピネフリン及びプロドラッグ組成物
US10792246B2 (en) 2018-06-27 2020-10-06 Bioxcel Therapeutics, Inc. Film formulations containing dexmedetomidine and methods of producing them
US20240024288A1 (en) 2019-07-19 2024-01-25 Bioxcel Therapeutics, Inc. Non-sedating dexmedetomidine treatment regimens
CA3180948A1 (en) * 2020-06-02 2021-12-09 Mohamed Hussein Hamdan Sublingual formulation for hypotension and syncope
US12286451B2 (en) 2020-11-23 2025-04-29 Medtech Products Inc. Borate ester complexes of α-hydroxy carboxylic acids and their conjugate base buffers
WO2023076281A1 (en) 2021-10-25 2023-05-04 Aquestive Therapeutics, Inc. Oral and nasal compositions and methods of treatment
US11806334B1 (en) 2023-01-12 2023-11-07 Bioxcel Therapeutics, Inc. Non-sedating dexmedetomidine treatment regimens

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3558768A (en) * 1969-12-19 1971-01-26 Sterling Drug Inc Sustained release pharmaceutical compositions
US4291015A (en) * 1979-08-14 1981-09-22 Key Pharmaceuticals, Inc. Polymeric diffusion matrix containing a vasodilator
US4427681A (en) * 1982-09-16 1984-01-24 Richardson-Vicks, Inc. Thixotropic compositions easily convertible to pourable liquids
US5025019A (en) * 1984-04-09 1991-06-18 Analgesic Associates Cough/cold mixtures comprising non-steroidal anti-inflammatory drugs
US4623664A (en) * 1985-10-31 1986-11-18 University Of Iowa Research Foundation Oil suspended phenylephrine
US4764378A (en) * 1986-02-10 1988-08-16 Zetachron, Inc. Buccal drug dosage form
US4792452A (en) * 1987-07-28 1988-12-20 E. R. Squibb & Sons, Inc. Controlled release formulation
US5085865A (en) * 1989-04-12 1992-02-04 Warner-Lambert Company Sustained release pharmaceutical preparations containing an analgesic and a decongestant
US5133974A (en) * 1989-05-05 1992-07-28 Kv Pharmaceutical Company Extended release pharmaceutical formulations
ATE118345T1 (de) * 1990-08-07 1995-03-15 Pfizer Verwendung von interfacial polymerisierten membranen in abgabevorrichtungen.
US5518730A (en) * 1992-06-03 1996-05-21 Fuisz Technologies Ltd. Biodegradable controlled release flash flow melt-spun delivery system
US5458879A (en) * 1994-03-03 1995-10-17 The Procter & Gamble Company Oral vehicle compositions
GB9422571D0 (en) * 1994-11-09 1995-01-04 Whitehall Lab Ltd Haemorrihoidal compositions and method of use
US5827531A (en) * 1994-12-02 1998-10-27 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Microcapsules and methods for making
NL1005394C1 (nl) * 1996-04-01 1997-10-02 Kokbing Lo Bevestigingselement en band bevestigd met bevestigingselement.
WO1998027971A1 (en) * 1996-12-23 1998-07-02 Michael Albert Kamm Pharmaceutical composition for treating fecal incontinence and anal itch
EP1021204B1 (en) * 1997-09-26 2005-12-28 Noven Pharmaceuticals, Inc. Bioadhesive compositions and methods for topical administration of active agents
US6602521B1 (en) * 1998-09-29 2003-08-05 Impax Pharmaceuticals, Inc. Multiplex drug delivery system suitable for oral administration
US7815937B2 (en) * 1998-10-27 2010-10-19 Biovail Laboratories International Srl Quick dissolve compositions and tablets based thereon
US6521254B2 (en) * 1998-12-07 2003-02-18 J-Med Pharmaceuticals, Inc. Single-dose antihistamine/decongestant formulations for treating rhinitis
US6267986B1 (en) * 1999-09-24 2001-07-31 Ranbaxy Laboratories Limited Process for the preparation of a controlled drug delivery system containing pseudoephedrine and a long acting antihistamine
US6114346A (en) * 1999-10-22 2000-09-05 Schering Corporation Treating sleep disorders using desloratadine
AU2276801A (en) * 1999-12-20 2001-07-03 Schering Corporation Extended release oral dosage composition
WO2001045668A2 (en) * 1999-12-20 2001-06-28 Schering Corporation Stable extended release oral dosage composition comprising pseudoephedrine and desloratadine
US6955821B2 (en) * 2000-04-28 2005-10-18 Adams Laboratories, Inc. Sustained release formulations of guaifenesin and additional drug ingredients
WO2001089476A1 (en) * 2000-05-19 2001-11-29 Npd Llc Chewing gums, lozenges, candies, tablets, liquids, and sprays for efficient delivery of medications and dietary supplements
WO2003009834A1 (en) * 2000-08-17 2003-02-06 Battey Alyce S Oral delivery of pharmaceuticals via encapsulation
US20030236275A1 (en) * 2002-06-20 2003-12-25 Schering Corporation Treatment methods of nasal congestion and nasal obstruction
US6585997B2 (en) * 2001-08-16 2003-07-01 Access Pharmaceuticals, Inc. Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds
WO2003019948A1 (en) * 2001-08-27 2003-03-06 Koninklijke Philips Electronics N.V. Video data processor
US7163696B2 (en) * 2001-10-11 2007-01-16 Pfizer Inc. Pharmaceutical formulations
US20030083354A1 (en) * 2001-10-26 2003-05-01 Pediamed Pharmaceuticals, Inc. Phenylephrine tannate and pyrilamine tannate salts in pharmaceutical compositions
US20030114535A1 (en) * 2001-12-14 2003-06-19 Jame Fine Chemicals, Inc. Dextrochlorpheniramine tannate
US20040122107A1 (en) * 2002-09-13 2004-06-24 Fine Jeffrey R Method of alleviating barometric-induced symptoms in airline passengers
JP2004121962A (ja) * 2002-10-01 2004-04-22 National Institute Of Advanced Industrial & Technology ナノバブルの利用方法及び装置
US6979689B2 (en) * 2002-12-20 2005-12-27 Pediamed Pharmaceuticals, Inc. Compositions and methods for treating upper respiratory congestion
US20040214215A1 (en) * 2003-03-07 2004-10-28 Yu Ruey J. Bioavailability and improved delivery of alkaline pharmaceutical drugs
US20050152967A1 (en) * 2003-03-28 2005-07-14 Pfab, Lp Dynamic variable release
US20050026890A1 (en) * 2003-07-31 2005-02-03 Robinson Cynthia B. Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with an antihistamine for treatment of asthma or chronic obstructive pulmonary disease
US20070219253A1 (en) * 2003-09-17 2007-09-20 Gul Balwani Decongestant / antihistaminic / expectorant compositions
US20050095288A1 (en) * 2003-11-03 2005-05-05 Andrx Labs, Llc Decongestant and expectorant tablets
US20050266032A1 (en) * 2003-12-17 2005-12-01 Sovereign Pharmaceuticals, Ltd. Dosage form containing multiple drugs
JP2007517806A (ja) * 2004-01-15 2007-07-05 オーラル バイオサイエンス ピーティーワイ. リミテッド 口腔用麻酔ゲル
CA2590834A1 (en) * 2004-12-13 2006-06-22 Mcneil-Ppc, Inc. Compositons and methods for stabilizing active pharmaceutical ingredients
US8318210B2 (en) * 2005-02-28 2012-11-27 Neos Therapeutics, Lp Compositions and methods of making sustained release liquid formulations
ES2398960T3 (es) * 2005-06-17 2013-03-22 Aft Pharmaceuticals Limited Composición farmacéutica novedosa y su uso en un método para el tratamiento de pacientes con cangestión mucosa de las vías respiratorias altas
US20070141147A1 (en) * 2005-12-21 2007-06-21 Auriga Laboratories, Inc. Sequential release pharmaceutical formulations
US8940796B2 (en) * 2006-02-21 2015-01-27 Wyeth Llc Phenylephrine liquid formulations
US20080014274A1 (en) * 2006-07-14 2008-01-17 Wyeth Enhanced stability phenylephrine liquid compositions
US9005652B2 (en) * 2006-07-25 2015-04-14 Wyeth Chewable tablet containing phenylephrine
US7378082B1 (en) * 2007-11-05 2008-05-27 Inspire Pharmaceuticals, Inc. Method for treating allergic rhinitis without adverse effects

Also Published As

Publication number Publication date
RU2010127737A (ru) 2012-01-20
EP2237767A1 (en) 2010-10-13
JP2011506337A (ja) 2011-03-03
CA2709208A1 (en) 2009-06-18
AR069572A1 (es) 2010-02-03
TW200932208A (en) 2009-08-01
WO2009076165A1 (en) 2009-06-18
BRPI0820673A2 (pt) 2015-06-16
MX2010006284A (es) 2010-09-07
CL2008003615A1 (es) 2009-10-16
AU2008335464A1 (en) 2009-06-18
PE20091084A1 (es) 2009-07-23
KR20100102632A (ko) 2010-09-24
US20090280160A1 (en) 2009-11-12
CN101938991A (zh) 2011-01-05
CO6321221A2 (es) 2011-09-20

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