WO1997047292A1 - Utilisation d'antagonistes de h2 pour preparer une composition topique pour le traitement des rhumes - Google Patents

Utilisation d'antagonistes de h2 pour preparer une composition topique pour le traitement des rhumes Download PDF

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Publication number
WO1997047292A1
WO1997047292A1 PCT/US1997/009977 US9709977W WO9747292A1 WO 1997047292 A1 WO1997047292 A1 WO 1997047292A1 US 9709977 W US9709977 W US 9709977W WO 9747292 A1 WO9747292 A1 WO 9747292A1
Authority
WO
WIPO (PCT)
Prior art keywords
use according
compound
ranitidine
colds
cimetidine
Prior art date
Application number
PCT/US1997/009977
Other languages
English (en)
Inventor
Robert Ernest Singer, Jr.
Original Assignee
The Procter & Gamble Company
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 The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to BR9709792A priority Critical patent/BR9709792A/pt
Priority to EP97928916A priority patent/EP0954294A1/fr
Priority to JP10501751A priority patent/JPH11513035A/ja
Priority to AU33069/97A priority patent/AU3306997A/en
Publication of WO1997047292A1 publication Critical patent/WO1997047292A1/fr

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine

Definitions

  • the present invention relates to a method of preventing or controlling colds and similar maladies, such as flu, through the use of an oral composition containing an H2 blocker applied to the gingival or oral mucosal tissue of the subject susceptible to colds.
  • the common cold although not usually a serious illness, is a highly prevalent, discomforting and annoying infliction.
  • the term "common cold” is applied to minor respiratory illnesses caused by a variety of different respiratory viruses. While rhinoviruses are the major known cause of common colds, accounting for approximately 30 percent of colds in adults, viruses in several other groups are also important. While immune responses occur, and infection with some respiratory tract viruses therefore could be prevented by a vaccine, development of a polytypic vaccine to cover all possible agents is impractical. Thus, the problem of controlling acute upper respiratory disease presents complex challenges, and the long-desired discovery of a single cure for the common cold is an unrealistic expectation.
  • compositions for treatment of nasal and other cold, flu, allergy and sinus symptoms and the discomfort, pain, fever and general malaise associated therewith generally contain an analgesic (aspirin or acetaminophen) and one or more antihistamines, decon- gestants, cough suppressants, antitussives and expectorants.
  • analgesic aspirin or acetaminophen
  • Other specific pharmaceutical actives for nasal symptoms e.g., congestion
  • These actives are generally delivered topically to the nasal mucosa via a nasal spray.
  • oral drugs such as decongestants could pose a risk of unfavorable drug interactions and may cause an adverse reaction. It would, therefore, be highly desirable to deliver relief from specific nasal symptoms via compositions without the need for such pharmaceutical actives. It has been discovered that topical application of an Hj antagonist compound to the gingival or oral mucosal tissues of a subject susceptible to colds and/or flu helps to reduce the incidence of such maladies.
  • the present invention relates to a method of reducing colds and cold-like symptoms, such as flu, in subjects susceptible to such maladies by applying a composition containing an effective amount of an H2 antagonist compound to the gingival or oral mucosal tissues.
  • compositions of the present invention contain certain essential components as well as non-essential components.
  • H2 antagonist compounds useful in the present invention include many different agents.
  • Preferred H2 antagonists include cimetidine, etintidine, ranitidine, ICIA-5165, tiotidine, ORF- 17578, luptidine, donetidine, famotidine, roxatidine, pifatidine, lamtidine, BL-6548, BMY-25271, zaltidine, nizatidine, mifentidine, BMY-52368, SKF-94482, BL-6341A, ICI- 162846, ramixotidine, Wy-45727, SR-58042, BMY- 25405, loxtidine, DA-4634, bisfentidine, sufotidine, ebrotidine, HE-30-256, D- 16637, FRG-8813, FRG-8701, impromidine, L-643728, and HB-4-08.
  • Cimetidine, ranitidine, famotidine, roxatidine, nizatidine, and mifentidine are more preferred and cimetidine and ranitidine are most preferred.
  • H2 antagonist compounds are used in an amount of from about 0.001% to about 40%, preferably from about 0.01% to about 20%, most preferably from about 0.1% to about 10%.
  • Acceptable Carrier The carrier for the active component(s) can be any vehicle suitable for use in the oral cavity. Such carriers include the usual components of mouthwashes, toothpastes, tooth powders, prophylaxis pastes, lozenges, gums and the like and are more fully described hereinafter. Dentifrices and mouthwashes are the preferred systems.
  • the present compositions may contain antiplaque/gingivitis agent such as quaternary ammonium compounds, water insoluble agents such as triclosan, teas, as defined herein later, stannous salts and zinc salts.
  • antiplaque/gingivitis agent such as quaternary ammonium compounds, water insoluble agents such as triclosan, teas, as defined herein later, stannous salts and zinc salts.
  • silicas including gels and precipitates, calcium carbonate, dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, insoluble sodium polymetaphosphate, hydrated alumina, and resinous abrasive materials such as particulate condensation products of urea and formaldehyde, and other such as disclosed by Cooley et al. in U.S. Patent 3,070,510, December 25, 1962, incorporated herein by reference. Mixtures of abrasives may also be used.
  • Silica dental abrasives of various types, can provide the unique benefits of exceptional dental cleaning and polishing performance without unduly abrading tooth enamel or dentin.
  • Silica abrasive materials are also exceptionally compatible with sources of soluble fluoride and polyphosphonates. For these reasons they are preferred for use herein.
  • the silica abrasive can be precipitated silica or silica gels such as the silica xerogels described in Pader et al., U.S. Patent No. 3,538,230, issued March 2, 1970 and DiGiulio, U.S. Patent No. 3,862,307, June 21, 1975, both incorporated herein by reference.
  • Preferred precipitated silica materials include those marketed by the J. M. Huber Corporation under the tradename, "Zeodent", particularly the silica carrying the designation "Zeodent 119". These silica abrasives are described in U.S. Patent No. 4,340,583, July 29, 1982, incorporated herein by reference.
  • the abrasive in the compositions described herein is present at a level of from about 6% to about 70%, preferably from about 15% to about 25% when the dentifrice is a toothpaste. Higher levels, as high as 90%, may be used if the composition is a toothpowder.
  • Flavoring agents can also be added to dentifrice compositions. Suitable flavoring agents include, among many others, oil of wintergreen, oil of peppermint, oil of spearmint, and oil of clove. Sweetening agents which can be used include aspartame, acesulfame, saccharin, dextrose, levulose and sodium cyclamate. Flavoring and sweetening agents are generally used in dentifrices at levels of from about 0.005% to about 2% by weight.
  • Dentifrice compositions can also contain emulsifying agents. Suitable emulsifying agents are those which are reasonably stable and foam throughout a wide pH range, including nonsoap anionic, nonionic, cationic, zwitterionic and amphoteric organic synthetic detergents. Many of these suitable surfactants are disclosed by Gieske et al. in U.S. Patent No. 4,051,234, September 27, 1977, incorporated herein in its entirety by reference.
  • Water is also present in the toothpastes of this invention.
  • Water employed in the preparation of commercially suitable toothpastes should preferably be deionized and free of organic impurities.
  • Water generally comprises from about 10% to 50%, preferably from about 20% to 40%, by weight of the toothpaste compositions herein. These amounts of water include the free water which is added plus that which is introduced with other materials such as with sorbitol.
  • Preferred thickening agents are carboxyvinyl polymers of the type mentioned previously herein, xanthan gum, carrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose.
  • Natural gums such as gum karaya, gum arabic, and gum tragacanth can also be used.
  • Colloidal magnesium aluminum silicate or finely divided silica can be used as part of the thickening agent to further improve texture.
  • Thickening agents in an amount from 0.5% to 5.0% by weight of the total composition can be used.
  • humectant material in a toothpaste to keep it from hardening.
  • Suitable humectants include glycerin, sorbitol, and other edible polyhydric alcohols at a level of from about 15% to about 70%.
  • Mouthwash composition is a mouthwash composition.
  • Conventional mouthwash composition components can comprise the carrier for the active agents of the present invention.
  • Mouthwashes generally comprise from about 20:1 to about 2: 1 of a water/ethyl alcohol solution and preferably other ingredients such as flavor, sweeteners, humectants and sudsing agents such as those mentioned above for dentifrices.
  • the humectants, such as glycerin and sorbitol give a moist feel to the mouth.
  • the mouthwashes of the invention comprise 0% to 60% (preferably 10% to 25%) ethyl alcohol, 0% to 20% (preferably 5% to 20%) of a humectant, 0% to 2% (preferably 0.01% to 0.15%) emulsifying agent, 0% to 0.5% (preferably 0.005% to 0.06%) sweetening agent such as saccharin, 0% to 0.3% (preferably 0.03% to 0.3%) flavoring agent, and the balance water.
  • Suitable lozenge and chewing gum components are disclosed in U.S. Patent No. 4,083,955, April 11, 1978 to Grabenstetter et al., incorporated herein by reference.
  • Other optional components useful in the present invention are pyrophosphate salts such as those described in U.S. 4,515,772, May 7, 1985 to Parran et al. incorporated herein by reference.
  • Also useful are nonionic antimicrobials such as triclosan described in U.S. 4,894,220, January 16, 1990 to Nabi et al. Both patents are incorporated herein by reference.
  • Another agent which can be used in the present compositions is an alkali metal bicarbonate, such as sodium bicarbonate.
  • compositions of the subject invention are controlled-release drug delivery systems for placement in the periodontal pocket.
  • Such systems include, but are not limited to, the cellulose hollow fibers disclosed in U.S. Pat. No. 4,175,326, issued to Goodson on Nov. 27, 1979; the ethylcellulose films disclosed in U.S. Pat. No. 4,568,535 issued to Loesche on Feb. 4, 1986; the absorbable putty- like material disclosed in U.S. Pat. No.
  • Such controlled-release delivery systems generally include a solid matrix, usually of polymeric material, loaded with one or more active agents, the matrix entrapping the H2 antagonists. Typically, the active agents diffuse from the wolid material into the periodontal pocket over time.
  • Preferred controlled-release drug delivery systems comprise from about 0.001% to about 50%, more preferably from about 0.01% to about 25%, more preferably still from about 0.1% to about 15%, still more preferably from about 1% to about 10%, of a H2 antagonist and a controlled-release carrier.
  • the pH of the present compositions and/or its pH in the mouth can be any pH which is safe for the mouth's hard and soft tissues. Such pH's are generally from about 3 to about 10, preferably from about 5 to about 9.
  • the carrier compositions of the present invention can be made using methods which are common in the oral products area.
  • toothpaste compositions may be prepared by mixing part of the humectant and water together and heating to 66°-71°C.
  • the fluoride source if present, is then added along with the sweetener, the opacifier and the flavor.
  • the cranberry extract may be combined with the glycerine prior to adding to the other components.
  • the present invention in its method aspect involves applying to the gingival and/or oral mucosal tissue safe and effective amounts of the compositions.
  • a preferred method of the subject invention involves the contact of a composition of the subject invention with oral cavity soft tissue afflicted with gingivitis or periodontitis for at least about 15 seconds, preferably from about 20 seconds to about 10 minutes, more preferably from about 30 seconds to about 60 seconds.
  • the method often involves expectoration of most of the composition following such contact, preferably followed by rinsing, e.g., with water.
  • the frequency of such contact is preferably from about once per week to about four times per day, more preferably from about thrice per week to about thrice per day, more preferably still from about once per day to about twice per day.
  • the period of such treatment typically ranges from about one day to a lifetime.
  • Famotidine 2.50
  • Peppermint Oil 0.80
  • mouthwash compositions of the subject invention are made by conventional processes by mixing the following:
  • An example of a dental solution of the subject invention is made by mixing the following:
  • Example 13 Ingredients (Wt * %)
  • Ethyl Cellulose Type N22 90 from Hercules, Inc. Mifentidine 10
  • the ethyl cellulose is dissolved in chloroform and then the mifentidine is added. The resulting mixture is cast on a glass plate. After evaporation of the chloroform, the residual film is removed from the plate and cut into pieces.
  • Example 14 Ingredients (Wt * %)

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cosmetics (AREA)

Abstract

Compositions orales pour application locale, contenant un antagoniste de H2, destinées à protéger contre les rhumes et la grippe.
PCT/US1997/009977 1996-06-12 1997-06-10 Utilisation d'antagonistes de h2 pour preparer une composition topique pour le traitement des rhumes WO1997047292A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
BR9709792A BR9709792A (pt) 1996-06-12 1997-06-10 Utilização de antagonistas h2 para a fabricação de uma composição tópica para o tratamento de resfriados
EP97928916A EP0954294A1 (fr) 1996-06-12 1997-06-10 Utilisation d'antagonistes de h2 pour preparer une composition topique pour le traitement des rhumes
JP10501751A JPH11513035A (ja) 1996-06-12 1997-06-10 風邪の治療用の局所用組成物の製造のためのｈ２拮抗剤の使用
AU33069/97A AU3306997A (en) 1996-06-12 1997-06-10 Use of h2-antagonists for the manufacture of a topical composition for the treatment of colds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US66238996A 1996-06-12 1996-06-12
US08/662,389 1996-06-12

Publications (1)

Publication Number Publication Date
WO1997047292A1 true WO1997047292A1 (fr) 1997-12-18

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Application Number Title Priority Date Filing Date
PCT/US1997/009977 WO1997047292A1 (fr) 1996-06-12 1997-06-10 Utilisation d'antagonistes de h2 pour preparer une composition topique pour le traitement des rhumes

Country Status (8)

Country Link
EP (1) EP0954294A1 (fr)
JP (1) JPH11513035A (fr)
CN (1) CN1221338A (fr)
AU (1) AU3306997A (fr)
BR (1) BR9709792A (fr)
CA (1) CA2257990A1 (fr)
ID (1) ID19099A (fr)
WO (1) WO1997047292A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001074780A1 (fr) * 2000-03-21 2001-10-11 Astion Development Aps Complexe chimique comprenant un derive de pyridine carboxy et un antagoniste du recepteur d'histamine h2
WO2002002096A2 (fr) * 2000-06-30 2002-01-10 The Procter & Gamble Company Renforcement global de l'organisme
WO2002002128A2 (fr) * 2000-06-30 2002-01-10 The Procter & Gamble Company Renforcement global de l'organisme
WO2003092692A1 (fr) * 2002-04-30 2003-11-13 Ucb, S.A. Agent therapeutique comprenant de la lafutidine
US6846478B1 (en) 1998-02-27 2005-01-25 The Procter & Gamble Company Promoting whole body health

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20031640A1 (it) * 2003-08-08 2005-02-09 Mipharm S P A Base per gel bioadesivi.

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4749700A (en) * 1984-10-23 1988-06-07 Nastech Pharmaceutical Co, Inc. Novel methods of administering antihistamines, antinausea and antiemetic pharmaceutical agents and novel dosage forms containing same
US5294433A (en) * 1992-04-15 1994-03-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis
US5373022A (en) * 1991-03-04 1994-12-13 The Warner-Lambert Company Salts/ion pairs of non-steroidal anti-inflammatory drugs in various dosage forms

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4749700A (en) * 1984-10-23 1988-06-07 Nastech Pharmaceutical Co, Inc. Novel methods of administering antihistamines, antinausea and antiemetic pharmaceutical agents and novel dosage forms containing same
US5373022A (en) * 1991-03-04 1994-12-13 The Warner-Lambert Company Salts/ion pairs of non-steroidal anti-inflammatory drugs in various dosage forms
US5294433A (en) * 1992-04-15 1994-03-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6846478B1 (en) 1998-02-27 2005-01-25 The Procter & Gamble Company Promoting whole body health
WO2001074780A1 (fr) * 2000-03-21 2001-10-11 Astion Development Aps Complexe chimique comprenant un derive de pyridine carboxy et un antagoniste du recepteur d'histamine h2
WO2002002096A2 (fr) * 2000-06-30 2002-01-10 The Procter & Gamble Company Renforcement global de l'organisme
WO2002002128A2 (fr) * 2000-06-30 2002-01-10 The Procter & Gamble Company Renforcement global de l'organisme
WO2002002128A3 (fr) * 2000-06-30 2002-04-25 Procter & Gamble Renforcement global de l'organisme
WO2002002096A3 (fr) * 2000-06-30 2002-09-12 Procter & Gamble Renforcement global de l'organisme
US8277782B2 (en) 2000-06-30 2012-10-02 The Procter & Gamble Company Topical oral care compositions comprising host response modulating agents
WO2003092692A1 (fr) * 2002-04-30 2003-11-13 Ucb, S.A. Agent therapeutique comprenant de la lafutidine

Also Published As

Publication number Publication date
CA2257990A1 (fr) 1997-12-18
JPH11513035A (ja) 1999-11-09
CN1221338A (zh) 1999-06-30
AU3306997A (en) 1998-01-07
ID19099A (id) 1998-06-11
EP0954294A1 (fr) 1999-11-10
BR9709792A (pt) 1999-08-10

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