[go: up one dir, main page]

WO1999038505A1 - Compositions pour la prevention et le traitement de symptomes de type rhume et grippe associes aux infections des voies respiratoires - Google Patents

Compositions pour la prevention et le traitement de symptomes de type rhume et grippe associes aux infections des voies respiratoires Download PDF

Info

Publication number
WO1999038505A1
WO1999038505A1 PCT/US1999/001400 US9901400W WO9938505A1 WO 1999038505 A1 WO1999038505 A1 WO 1999038505A1 US 9901400 W US9901400 W US 9901400W WO 9938505 A1 WO9938505 A1 WO 9938505A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
compound
hydrogen
composition
respiratory tract
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/US1999/001400
Other languages
English (en)
Inventor
Nicholas Seymour Gantenberg
Haruko Mizoguchi
Robert Ernest Singer, Jr.
Ronald Lee Smith
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.)
Procter and Gamble Co
Original Assignee
Procter and Gamble Co
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 Procter and Gamble Co filed Critical Procter and Gamble Co
Priority to AU24663/99A priority Critical patent/AU2466399A/en
Priority to JP2000529238A priority patent/JP2002527351A/ja
Publication of WO1999038505A1 publication Critical patent/WO1999038505A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • A61P11/04—Drugs for disorders of the respiratory system for throat disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals

Definitions

  • the present invention is for compositions and their methods for prevention and treatment of cold and influenza-like symptoms due to respiratory tract infections. These compounds and their method of application are effective in both preventing the onset of the symptoms of colds and influenza or significantly mitigating them if already afflicted with such symptoms. BACKGROUND SUMMARY OF THE ART
  • cough/cold products typically contain one or more of the following actives: nasal decongestants such as pseudoephedrine, oxymetazoline, antihistamines such as doxylamine, antitussives such as dextromethorphan, expectorants such as guaifenesin and antipyretics such as acetaminophen.
  • nasal decongestants such as pseudoephedrine, oxymetazoline
  • antihistamines such as doxylamine
  • antitussives such as dextromethorphan
  • expectorants such as guaifenesin
  • antipyretics such as acetaminophen.
  • Examples of these therapies include the use of interferon- ⁇ 2 , see Douglas et al., Prophylactic Efficacy of Intranasal Alpha - Interferon against Rhinovirus Infection in the Family Setting. The New England Journal of Medicine, 314, pp. 65-70, 1986; bradykinin antagonist, see Higgins et al., A Study of the Efficacy of the Brandvkinin Antagonist, NPC567. in Rhinovirus Infections in Human Volunteers. Antiviral Research vol. 14, pp.
  • glucocorticoid see Farr et al., A Randomized Controlled Trial of Glucocorticoid Prophylaxis against Experimental Rhinovirus Infection, The Journal of Infectious Diseases vol. 162, pp. 1173-1177, 1990; nedocromil, see Barrow et al., The Effect of Intranasal Nedocromil Sodium on Viral Upper Respiratory Tract
  • a number of patents have also been issued disclosing compositions for prevention and treatment of the common cold and their methods of use.
  • a sample of such patents include: US Patents 5,240,694; 5,422,097; and 5,492,689; all to Gwaltney, disclosing treatment using combinations of anti-viral and anti- inflammatory compounds; US Patents Re 33,465 and 5,409,905; both to Eby disclosing treatment using zinc salts; US Pat. 5,626,831; to Van Moerkerken disclosing treatments using orally administered aminocarboxylic acid compounds; U.S.
  • compositions and preventative treatments known in the art, there remains a need to provide a consistent and effective method for prevention and treatment of cold and influenza symptoms.
  • the present invention is for respiratory tract compositions and methods for using such compositions for prevention and treatment of cold and influenza-like symptoms due to respiratory tract infections. These methods include the administration of an respiratory tract composition comprising compounds conforming to the following chemical structure: R O
  • Respiratory tract compositions refers to compositions in a form that is directly deliverable to the airway passages from the nose and mouth. These compositions include, but are not limited to droppers, pump sprayers, pressurized sprayers, atomizers, air inhalation devices and other packaging and equipment known or yet to be developed.
  • Cold and influenza-like symptoms refers to symptoms typically associated with respiratory tract viral infections. These symptoms include, but not limited to nasal congestion, chest congestion, sneezing, rhinorrhea, fatigue or malaise, coughing, fever, chills, body ache, sore throat and headache and other known cold and influenza-like symptoms.
  • “Pharmaceutically acceptable vehicle” refers to any solid, liquid or gas combined with compound in the composition of the present invention to deliver the compound to the respiratory tract of the user. These vehicles are generally regarded as safe for use in humans. DETAILED DISCUSSION OF THE INVENTION
  • the present invention is for respiratory tract compositions and the methods of using said compositions for preventing or treating the cold and influenza-like symptoms associated with respiratory tract infections.
  • the method provides for administering a composition into the respiratory tract comprising compounds conforming to the following chemical structure:
  • R is selected from the group consisting hydrogen (-H); hydroxyl group (OH); ester groups having the structure -OCOR" wherein R" is selected from the group consisting of C , to C 18 branched and straight chained alkyl groups, non- substituted aryl groups, aryl groups substituted with chlorine (-C1), fluorine (-F) bromine (-Br), a hydroxyl group (-OH), a carboxyl group (-COOH), groups having the structure -OR'" and -COOR'" wherein R'" is selected from the group consisting of branched and straight chained alkyl groups having from 1 to about 4 carbon atoms; X is selected from the group consisting of oxygen (-O) and nitrogen (-N); and R' is selected from the group consisting of hydrogen (-H); two hydrogen atoms (-H 2 ); and R".
  • These compounds can also be in the form of a free base or salt.
  • salts include but not limited to those formed by addition of maleic acid, hydrogen chloride, hydrogen bromide, EDTA, tartaric acid and mixtures thereof.
  • Preferred compounds used in the present invention include the above structures wherein R is selected from the group consisting of -OH, -OCOR" and -H, X is -O and R' is selected from the group consisting of -H, and R". Most preferred is where R is -OH, X is -O and R' is -H.
  • Such a preferred compounds is 3-carboxy- 2-hydroxy-N,N,N-trimethyl-l-propanaminium hydroxide, inner salt; see Merck Index. 10 th Ed., 1983, at p. 257.
  • Said compound is also known in the art as L- carnitine or levocarnitine.
  • L-carnitine is commercially available from Lonza Ltd. Basel, Switzerland.
  • L-carnitine is known in the art for acute treatment of patients with an inborn error of metabolism that results in secondary carnitine deficiency, primary systemic carnitine deficiency and dietary supplement for renal patients; see
  • L-carnitine is also known for use in commercially available products marketed as dieting aids, special diet foods and meal replacements, sports aids and general nutritional support. Typically it is found as one of the ingredients in a multi-component product in the solid or liquid form (tablets, capsules, tonics, beverages) to be ingested orally.
  • the inner salt of 3-carboxy-2-hydroxy-N,N,N-trimethyl-l-propanaminium hydroxide or L-carnitine may be structurally modified to yield esters. Synthetic reactions for producing such esters are those that are routinely practiced one skilled in the chemical arts.
  • L-carnitine inner salt esters have carboxyl groups esterified with a compound selected from the group consisting of alpha, beta, gamma and delta tocopherol; 1,2- dimethyl-3-hydroxypyrid-4-one; (S)(-)6-hydroxy-2,5,7,8-tetramethylchroman-2- carboxylic acid or mixture of (S)(-) and (R)(+)6-hydroxy-2,5,7,8- tetramethylchroman-2-carboxylic acid.
  • L-carnitine esters useful in the present invention include those having the hydroxyl group of the above compound esterified with ascorbic acid, (S)(-)6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid or mixture of (S)(-) and (R)(+)6-hydroxy-2,5J,8-tetramethylchroman-2-carboxylic acid.
  • the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid is available as "Trolox" from Aldrich Chemical Company.
  • These later types of esters can be further esterified at the carboxyl group with R".
  • the absolute configuration and enantiomer designation of these compounds are defined using the established terminology "S and R" and "+ and -", respectively, see Dean, Handbook of Organic Chemistry, PP. 1-48, 1-51, 1987.
  • the level of the above-described compounds varies with its compositional form.
  • the level of the compound ranges from about 0.01% to about 50%, preferably from about 0.05% to about 20% and most preferably from about 0.1% to about 5% of the composition.
  • the level of the compound in said composition ranges from about 0.01% to 100%, preferably from about 0.1% to about 99% and most preferably from about 20% to about 90% of the composition.
  • compositions of the present invention may include a pharmaceutical acceptable vehicle.
  • compositions of the present invention include aqueous buffered solutions or dispersions; aqueous buffered solutions or dispersions containing co-solvents such as ethanol, propylene glycol, water-miscible solvent; liquid aerosol propellants and mixtures thereof.
  • these vehicles have an osmotic pressure that is about equal to that of human plasma and a pH approximately that of typical nasal secretions for use in intranasal products or the environment of the lungs for use in inhalation products.
  • the vehicle may also contain buffers for pH stability, preservatives to prevent inoculating dosing devices inserted into the nose with microorganisms.
  • Volatile oils, sensates and flavors may also be included to provide desirable in-use smell and taste of the composition.
  • the vehicle may also contain surfactants to aid in spreading the composition throughout the respiratory tract. Gums, mucilages, thickeners, mucoadhesive polymers and mixtures thereof may be included in order to slow the normal physiologic clearance of the solution from the nasal cavity to the oropharynx.
  • the composition of the present invention is in the form of a liquid
  • the vehicle is used in a level from about 50% to about 99.99%, preferably from about 80% to about 99.95% and most preferably from about 95% to about 99.9% of the treatment composition.
  • composition of the present invention is a solid form
  • vehicle may be applied in a powder form without use of a specific vehicle.
  • vehicles are often added to aid in processing of the compounds, providing acceptable flowability and particle size for inhalant application.
  • Other paniculate or powdered pharmaceutically acceptable filler materials may be combined with compounds of the present invention to facilitate flowability, stability, handling, hygroscopicity; favorable flavor, taste and, or sensation.
  • the solid vehicle is from 0% to about 99.99%, preferably from about 1% to about 99.9% and most preferably from about 10% to about 80% of the composition.
  • EXAMPLES The following are non-limiting examples of compositions of the present invention. All ingredients are by weight of 100 grams of the composition:
  • Example: 1 Intranasal spray solution 1.00 grams L-carnitine free base 0J0 grams nonionic detergent ' 0.11 grams dibasic sodium phosphate 0.38 grams monobasis potassium phosphate
  • Flavoring used at a level in order to provide a pleasing taste.
  • Flavoring used at a level in order to provide a pleasing taste.
  • Example 3 Intranasal powder:

Landscapes

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

Abstract

La présente invention porte sur des compositions utilisées dans la prévention et le traitement de symptômes tels que le rhume ou la grippe associés aux infections des voies respiratoires. L'invention porte également sur les procédés d'utilisation de ces compositions.
PCT/US1999/001400 1998-01-30 1999-01-22 Compositions pour la prevention et le traitement de symptomes de type rhume et grippe associes aux infections des voies respiratoires Ceased WO1999038505A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU24663/99A AU2466399A (en) 1998-01-30 1999-01-22 Compositions for prevention and treatment of cold and influenza-like symptoms associated with respiratory tract infections
JP2000529238A JP2002527351A (ja) 1998-01-30 1999-01-22 気道感染に関連した風邪及びインフルエンザ様症状の予防及び治療用組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US1625498A 1998-01-30 1998-01-30
US09/016,254 1998-01-30

Publications (1)

Publication Number Publication Date
WO1999038505A1 true WO1999038505A1 (fr) 1999-08-05

Family

ID=21776180

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/001400 Ceased WO1999038505A1 (fr) 1998-01-30 1999-01-22 Compositions pour la prevention et le traitement de symptomes de type rhume et grippe associes aux infections des voies respiratoires

Country Status (5)

Country Link
JP (1) JP2002527351A (fr)
AU (1) AU2466399A (fr)
CO (1) CO5050326A1 (fr)
PE (1) PE20000262A1 (fr)
WO (1) WO1999038505A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005009352A3 (fr) * 2003-07-17 2007-11-29 Univ Columbia Compostions antimicrobiennes contenant des combinaisons synergiques de composes d'ammonium quaternaire et d'huiles essentielles et/ou de leurs constituants
US7435429B2 (en) 2002-02-07 2008-10-14 Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
US7563461B2 (en) 2002-02-07 2009-07-21 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
US7879365B2 (en) 2002-02-07 2011-02-01 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
USRE45435E1 (en) 2002-02-07 2015-03-24 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6846846B2 (en) 2001-10-23 2005-01-25 The Trustees Of Columbia University In The City Of New York Gentle-acting skin disinfectants

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE660039A (fr) * 1965-02-22 1965-08-23
WO1989011276A1 (fr) * 1988-05-26 1989-11-30 Bernardini, Attilio Acyl-carnitine pour le traitement et la prevention d'infections virales
EP0681839A2 (fr) * 1994-05-12 1995-11-15 Hirohiko Kuratsune Préparation pharmaceutique renfermant une acylcarnitine
US5626831A (en) * 1995-12-20 1997-05-06 Van Moerkerken; Arthur Method for relief and prevention of common cold, and compositions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE660039A (fr) * 1965-02-22 1965-08-23
WO1989011276A1 (fr) * 1988-05-26 1989-11-30 Bernardini, Attilio Acyl-carnitine pour le traitement et la prevention d'infections virales
EP0681839A2 (fr) * 1994-05-12 1995-11-15 Hirohiko Kuratsune Préparation pharmaceutique renfermant une acylcarnitine
US5626831A (en) * 1995-12-20 1997-05-06 Van Moerkerken; Arthur Method for relief and prevention of common cold, and compositions

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DAL NEGRO ET AL: "L-carnitine and rehabilitative respiratory physiokinesitherapy: metabolic and ventilatory response in chronic respiratory insufficiency", INT J OF CLIN PARMACOL, THERAP AND TOXICOL, vol. 24, no. 8, 1986, pages 453 - 456, XP002103369 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7435429B2 (en) 2002-02-07 2008-10-14 Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
US7563461B2 (en) 2002-02-07 2009-07-21 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
US7879365B2 (en) 2002-02-07 2011-02-01 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
USRE45435E1 (en) 2002-02-07 2015-03-24 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
WO2005009352A3 (fr) * 2003-07-17 2007-11-29 Univ Columbia Compostions antimicrobiennes contenant des combinaisons synergiques de composes d'ammonium quaternaire et d'huiles essentielles et/ou de leurs constituants
AU2004258899B2 (en) * 2003-07-17 2009-09-03 The Trustees Of Columbia University In The City Of New York Antimicrobial compositons containing synergistic combinations of quaternary ammonium compounds and essential oils and/or constituents thereof
US9421263B2 (en) 2003-07-17 2016-08-23 The Trustees Of Columbia University In The City Of New York Antimicrobial compositions containing synergistic combinations of quaternary ammonium compounds and essential oils and/or constituents thereof

Also Published As

Publication number Publication date
CO5050326A1 (es) 2001-06-27
PE20000262A1 (es) 2000-06-02
JP2002527351A (ja) 2002-08-27
AU2466399A (en) 1999-08-16

Similar Documents

Publication Publication Date Title
JP4365106B2 (ja) 医薬配合剤
CA2334411C (fr) Utilisation d'une composition comprenant du formoterol et du budesonide pour la prevention ou le traitement d'un etat aigu d'asthme
AU777549B2 (en) Compositions for prevention and treatment of cold and influenza-like symptoms and their methods of use
US8367734B1 (en) Stable epinephrine suspension formulation with high inhalation delivery efficiency
AU764126B2 (en) Storable active substance concentrate with formoterol
TW470647B (en) Composition and pharmaceutical combination kit comprising formoterol and budesonide
KR970704422A (ko) 투여용 약제학적 조성물
CZ20033580A3 (cs) Aerosolový prostředek
BG65350B1 (bg) Стабилен концентрат на формотерол
JP2774379B2 (ja) 医薬エアロゾール組成物ならびにそれらのウイルス疾患の治療および予防用途
JP2000508675A (ja) 新規製剤
EA013351B1 (ru) Фармацевтические препараты, содержащие бета-агонист длительного действия, для введения путем распыления
RU2339403C2 (ru) Композиции для профилактики и лечения симптомов, подобных симптомам простуды и гриппа, содержащие выбранные склеивающиеся со слизистой полимеры, и способы лечения
CN1972730A (zh) 格隆溴铵用于治疗儿童哮喘
EA018589B1 (ru) Применение композиции, содержащей формотерол и дипропионат беклометазона, для предотвращения и/или лечения обострения астмы
CN107205936A (zh) 包含至少一种通过喷雾干燥得到的增加制剂稳定性的干粉的组合物
WO2007145866A1 (fr) Traitement antibiotique de fibrose kystique par livraison à jet rotatif
JP2010501612A (ja) 真菌感染の処置用医薬組成物
WO1992014466A1 (fr) Compositions pharmaceutiques antitussives
WO1999038505A1 (fr) Compositions pour la prevention et le traitement de symptomes de type rhume et grippe associes aux infections des voies respiratoires
DE69527713T2 (de) Verbindunngen und zusammensetzungen zur verabreichung via inhalation und insufflierung
MXPA05001901A (es) Composiciones para inhalacion con altas proporciones de medicamento.
JP2023520703A (ja) コロナウイルス感染症の防止および治療における使用のためのシアル酸組成物
CN113350323A (zh) 一种用于抑制冠状病毒的吸入剂及其制备方法和应用
TWI762449B (zh) 噴霧器用組成物

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AT AU AZ BA BB BG BR BY CA CH CN CU CZ CZ DE DE DK DK EE EE ES FI FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SK SL TJ TM TR TT UA UG UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
NENP Non-entry into the national phase

Ref country code: KR

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 529238

Kind code of ref document: A

Format of ref document f/p: F

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase