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WO1996009829A1 - Ameliorations d'excipients pour application locale par voie muqueuse - Google Patents

Ameliorations d'excipients pour application locale par voie muqueuse Download PDF

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Publication number
WO1996009829A1
WO1996009829A1 PCT/US1995/012288 US9512288W WO9609829A1 WO 1996009829 A1 WO1996009829 A1 WO 1996009829A1 US 9512288 W US9512288 W US 9512288W WO 9609829 A1 WO9609829 A1 WO 9609829A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
oil
aqueous matrix
therapeutic agent
mucosal
Prior art date
Application number
PCT/US1995/012288
Other languages
English (en)
Inventor
David W. Osborne
Original Assignee
Virotex Corporation
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 Virotex Corporation filed Critical Virotex Corporation
Priority to AU37263/95A priority Critical patent/AU3726395A/en
Publication of WO1996009829A1 publication Critical patent/WO1996009829A1/fr

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Classifications

    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Definitions

  • This present invention relates to topical carrier compositions which are capable of adhering to mucosal surfaces and which resist dissolution and/or erosion upon exposure to moisture. More specifically, the present invention relates to topical carrier compositions which may be used as vehicles for therapeutic agents in mucosal lesion treatments.
  • mucosal diseases are characterized by lesions localized on mucosal surfaces, particularly oral mucosal membranes such as buccal and gingival epithelium. These diseases include lichen planus, Behcet's syndrome, and canker sores. More generalized conditions, such as oral candidiasis, are also frequently encountered.
  • the present invention comprises a topical semisolid composition for use on mucosal membranes.
  • the composition comprises one or more hydrophilic polymers suspended in a non-aqueous matrix.
  • the hydrophilic polymer is cellulose gum, hydroxyethylcellulose, cross- linked acrylic acid polymers, PVM/PA copolymers, or combinations thereof.
  • the non-aqueous matrix is petrolatum, mineral oil, or combinations thereof. In still another embodiment, the non-aqueous matrix is a triglyceride. In another embodiment the non-aqueous matrix is a natural oil such as olive oil, peanut oil, almond oil, corn oil, or vegetable oil.
  • the composition further comprises a therapeutic agent such as a local anesthetic, a corticosteroid, an antimicrobial or an antifungal.
  • a therapeutic agent such as a local anesthetic, a corticosteroid, an antimicrobial or an antifungal.
  • the present invention is directed to novel, topical carrier compositions which may be applied to mucosal surfaces wherein the compositions are capable of forming a multi-layered coating over the treated mucosal site upon initial contact with moisture, wherein the coating comprises a hydrated adhesive layer proximate the mucosal surface, a non-aqueous matrix layer, and a hydrated top-coat film, and wherein said coating resists dissolution and/or erosion upon further contact with moisture.
  • the carrier compositions of the present invention comprise suspensions of rapidly hydrating hydrophilic polymers in non-aqueous matrices. As formulated, these compositions exhibit non-adhering, gel-like properties. However, upon contact with water, the exposed surfaces of the compositions are quickly hydrated to form a sealed, water-retardant film. The film resists further hydration within the non-aqueous matrix. Furthermore, if the composition is contacted with a moist surface, an adhesive, water-retardant seal is formed between the composition and the surface such that the composition becomes fixedly disposed on the site.
  • the present invention is highly effective in both adhering to mucosal surfaces and resisting dissolution and/or erosion upon exposure to moisture, due to the water- retardant film which forms around the carrier composition.
  • the hydrophilic polymer constituent of the compositions of the present invention may comprise, for example, calcium/sodium PVM/MA copolymer (commercially available as Gantrez MS-955 produced by GAF), Cellulose Gum (commercially available as CMC produced by Aqualon), hydroxyethylcellulose (commercially available as Natrosol produced by Aqualon), cross-linked acrylic acid polymers (such as the commercially available product Carbopol, produced by Goodrich), or PVM/MA copolymer (such as the commercially available product Stabileze, produced by ISP), or any combinations thereof.
  • calcium/sodium PVM/MA copolymer commercially available as Gantrez MS-955 produced by GAF
  • Cellulose Gum commercially available as CMC produced by Aqualon
  • hydroxyethylcellulose commercially available as Natrosol produced by Aqualon
  • cross-linked acrylic acid polymers such as the commercially available product Carbopol, produced by Goodrich
  • PVM/MA copolymer such as the commercial
  • the non-aqueous matrix component of the compositions of the present invention may comprise petrolatum, mineral oil, triglyceride, or a mixture of oils derived from natural sources, i.e. , olive oil, peanut oil, almond oil, corn oil, or vegetable oil.
  • the non-aqueous matrix may also comprise a mixture of the above compounds.
  • the hydrophilic polymer or combination of polymers as described above is preferably present in an amount equal to 2% to 40 weight percent of the overall composition.
  • the nonaqueous matrix comprises the remainder of the formulation, i.e. , about 60% to 98% by weight.
  • the present invention may be used as a carrier for therapeutic agents, especially medicinal agents used in the treatment of mucosal lesions.
  • therapeutic agents especially medicinal agents used in the treatment of mucosal lesions.
  • typical therapeutic agents include local anesthetics, corticosteroids, destructive therapy agents, antimicrobials and antifungals.
  • Some preferred concentrations of therapeutic agents are as follows:
  • tetracaine for local anesthetics such as tetracaine, tetracaine hydrochloride, lidocaine, lidocaine hydrochloride, dyclonine hydrochloride, dimethisoquin hydrochloride, dibucaine, dibucaine hydrochloride.
  • tetracaine for local anesthetics such as tetracaine, tetracaine hydrochloride, lidocaine, lidocaine hydrochloride, dyclonine hydrochloride, dimethisoquin hydrochloride, dibucaine, dibucaine hydrochloride.
  • butamben picrate and pramoxine hydrochloride a preferred concentration is about 0.025 % to 5% by weight of the total composition.
  • benzocaine a preferred concentration is about 2% to 25 % by weight;
  • corticosteroids such as betamethasone dipropionate, fluocinolone acetonide, betamethasone valerate, triamcinolone acetonide, clobetasol propionate, desoximetasone, diflorasone diacetate, amcinonide, flurandrenolide, hydrocortisone valerate, hydrocortisone butyrate, and desonide
  • a preferred concentration is about 0.01 % to 1.0% by weight.
  • Corticosteroids such as hydrocortisone or methylprednisolone acetate are preferably present in concentrations of about 0.2% to about 5.0% by weight.
  • Destructive therapy agents such as salicylic acid or lactic acid would preferably comprise about 2% to about 40% by weight of the composition.
  • Cantharidin is preferably utilized in a concentration of about 0.1 % to about 2.0% , and podophyllin would preferably be used in a concentration of about 5 % to about 30% by weight.
  • Some typical antimicrobials and antifungals and their preferred weight concentrations include: silver sulfadiazine (0.2% to 5.0%), oxiconazole nitrate (0.1 % to 5.0%). ciclopirox olamine (0.1 % to 5.0%), ketoconazole (0.1 % to 5.0%), miconazole nitrate (0.1 % to 5.0%), butoconazole nitrate (0.1 % to 5.0%), neomycin (0.1 % to 2.0%), gramicidin (0.01 % to 0.1 %), chlortetracycline hydrochloride (1.0% to 5.0%), meclocycline sulfosal icy late (0.2% to 4.0%), oxytetracycline (1.0% to 5.0%), and tetracycline hydrochloride (0.05 % to 5.0%). Additionally, about 2.000 to about 10.000 units of Polymyxin B, or about 200 to about 1,000 units of bacitracin may be utilized.
  • the agents may be combined with the non-aqueous matrix of the present invention by any means known to those skilled in the art. Thereafter, the therapeutic topical composition may be applied to particular mucosal sites requiring treatment. Upon contact with water, such as from saliva, the composition will adhere to the mucosal site and form a protective, water-retardant film on all surfaces exposed to the moisture such that the therapeutic agents within the composition are available for delivery to the mucosal site for an extended period of time.
  • the carrier compositions of the present invention may be combined with any local anesthetic known in the art for treatment of canker sores and/or lesions produced by Behcet's syndrome.
  • the carrier compositions may be combined with corticosteroid or cyclosporin A for the treatment of lichen planus.
  • Example 1 To further illustrate the present invention, but not by way of limitation, the following examples are provided.
  • Example 1 To further illustrate the present invention, but not by way of limitation, the following examples are provided.

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  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Physiology (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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition semi-solide pour application locale sur les membranes muqueuses, laquelle composition comprend un ou plusieurs polymères hydrophiles en suspension dans une matrice non aqueuse. Cette composition peut être combinée à un agent thérapeutique pour favoriser la guérison des lésions muqueuses.
PCT/US1995/012288 1994-09-27 1995-09-26 Ameliorations d'excipients pour application locale par voie muqueuse WO1996009829A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU37263/95A AU3726395A (en) 1994-09-27 1995-09-26 Improved topical carriers for mucosal applications

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US31341894A 1994-09-27 1994-09-27
US08/313,418 1994-09-27

Publications (1)

Publication Number Publication Date
WO1996009829A1 true WO1996009829A1 (fr) 1996-04-04

Family

ID=23215611

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/012288 WO1996009829A1 (fr) 1994-09-27 1995-09-26 Ameliorations d'excipients pour application locale par voie muqueuse

Country Status (2)

Country Link
AU (1) AU3726395A (fr)
WO (1) WO1996009829A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2319726A (en) * 1996-11-12 1998-06-03 Procter & Gamble Polymyxin A, B, C, D or E containing compositions for the treatment of periodontal disease, plaque and breath malodor
WO1998020842A3 (fr) * 1996-11-12 1998-06-25 Procter & Gamble Compositions de polymyxine et procedes de traitement de la parodontopathie et de la mauvaise haleine
WO2001028515A1 (fr) * 1999-10-22 2001-04-26 Líf-Hlaup ehf. Bio-Gels Pharmaceuticals Inc. Composition pharmaceutique pour le traitement de l'ulceration et/ou erosion epitheliale des muqueuses
WO2002064113A1 (fr) * 2001-02-15 2002-08-22 Access Pharmaceuticals, Inc. Formulations liquides pour la prevention et le traitement d'affections et de troubles des muqueuses
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
GB2392384A (en) * 2002-08-28 2004-03-03 Diomed Dev Ltd Compositions for topical application
WO2005116657A2 (fr) 2004-05-24 2005-12-08 Universität Zu Köln Identification d'un transporteur d'ergothioneine et ses utilisations therapeutiques
US7544348B2 (en) 2001-02-15 2009-06-09 Access Pharmaceuticals, Inc. Liquid formulations for the prevention and treatment of mucosal diseases and disorders
US7592458B2 (en) 2006-07-21 2009-09-22 Wright George E Dermal anesthetic compounds and pharmaceutical compositions for inducing local anesthesia and mitigating neuropathic pain
US7718674B2 (en) 2004-09-27 2010-05-18 Bridge Pharma, Inc. Methods of relieving neuropathic pain with the S-isomer of 2-{2[N-(2-indanyl)-N-phenylamino]ethyl}piperidine
EP2211896B1 (fr) 2007-11-13 2018-01-03 Meritage Pharma, Inc. Compositions pour le traitement de l'inflammation gastro-intestinale
US11622953B2 (en) * 2019-03-12 2023-04-11 Antoine VARANI Oral composition for the treatment of canker sores

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Volume 112, Number 11, issued 12 March 1990, YANGI et al., "Destabilization of Herpes Simplex Virus Type 1 Virions by Local Anesthetics, Alkaline pH and Calcium Depletion", page 63, Abstract No. 112:91623a. *
CHEMICAL ABSTRACTS, Volume 117, No. 19, issued 07 September 1992, POPP, "Antiwart Compositions Containing Keratolytic Agents", page 62, Abstract No. 117:97356r. *
GENNARO et al., "Remington's Pharmaceutical Sciences", Published 1985, by MACK PUBLISHING CO. (EASTON, PA), pages 805, 1285, 1295, 1298, 1301, 1302. *
WINDHOLZ et al., "The Merck Index", Published 1982, by MERCK & CO., INC. (RAHWAY, NJ), Numbers 7661, 5310, 2748, 2510, 212. *

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998020842A3 (fr) * 1996-11-12 1998-06-25 Procter & Gamble Compositions de polymyxine et procedes de traitement de la parodontopathie et de la mauvaise haleine
GB2319726A (en) * 1996-11-12 1998-06-03 Procter & Gamble Polymyxin A, B, C, D or E containing compositions for the treatment of periodontal disease, plaque and breath malodor
WO2001028515A1 (fr) * 1999-10-22 2001-04-26 Líf-Hlaup ehf. Bio-Gels Pharmaceuticals Inc. Composition pharmaceutique pour le traitement de l'ulceration et/ou erosion epitheliale des muqueuses
EP1997478A3 (fr) * 2001-02-15 2008-12-10 Access Pharmaceuticals, Inc. Formulations liquides pour la prévention et le traitement de maladies et troubles de la muqueuse
WO2002064113A1 (fr) * 2001-02-15 2002-08-22 Access Pharmaceuticals, Inc. Formulations liquides pour la prevention et le traitement d'affections et de troubles des muqueuses
US7547433B2 (en) 2001-02-15 2009-06-16 Access Pharmaceuticals, Inc. Liquid formulations for the prevention and treatment of mucosal diseases and disorders
US7544348B2 (en) 2001-02-15 2009-06-09 Access Pharmaceuticals, Inc. Liquid formulations for the prevention and treatment of mucosal diseases and disorders
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
GB2392384B (en) * 2002-08-28 2004-08-11 Diomed Dev Ltd Compositions for topical application
GB2392384A (en) * 2002-08-28 2004-03-03 Diomed Dev Ltd Compositions for topical application
WO2005116657A2 (fr) 2004-05-24 2005-12-08 Universität Zu Köln Identification d'un transporteur d'ergothioneine et ses utilisations therapeutiques
US7718674B2 (en) 2004-09-27 2010-05-18 Bridge Pharma, Inc. Methods of relieving neuropathic pain with the S-isomer of 2-{2[N-(2-indanyl)-N-phenylamino]ethyl}piperidine
US7592458B2 (en) 2006-07-21 2009-09-22 Wright George E Dermal anesthetic compounds and pharmaceutical compositions for inducing local anesthesia and mitigating neuropathic pain
EP2211896B1 (fr) 2007-11-13 2018-01-03 Meritage Pharma, Inc. Compositions pour le traitement de l'inflammation gastro-intestinale
EP3354276B1 (fr) 2007-11-13 2020-01-01 Meritage Pharma, Inc. Compositions pour le traitement de l'inflammation gastro-intestinale
US11622953B2 (en) * 2019-03-12 2023-04-11 Antoine VARANI Oral composition for the treatment of canker sores

Also Published As

Publication number Publication date
AU3726395A (en) 1996-04-19

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