WO1996009829A1 - Ameliorations d'excipients pour application locale par voie muqueuse - Google Patents
Ameliorations d'excipients pour application locale par voie muqueuse Download PDFInfo
- 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
Links
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.
Landscapes
- 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.
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)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998020842A2 (fr) * | 1996-11-12 | 1998-05-22 | The Procter & Gamble Company | 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 |
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 |
-
1995
- 1995-09-26 WO PCT/US1995/012288 patent/WO1996009829A1/fr active Application Filing
- 1995-09-26 AU AU37263/95A patent/AU3726395A/en not_active Abandoned
Non-Patent Citations (4)
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 (17)
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 |
WO1998020842A2 (fr) * | 1996-11-12 | 1998-05-22 | The Procter & Gamble Company | 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 |
US7547433B2 (en) | 2001-02-15 | 2009-06-16 | Access Pharmaceuticals, Inc. | Liquid formulations for the prevention and treatment of mucosal diseases and disorders |
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 |
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 |
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 |
GB2392384A (en) * | 2002-08-28 | 2004-03-03 | Diomed Dev Ltd | Compositions for topical application |
GB2392384B (en) * | 2002-08-28 | 2004-08-11 | 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 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0275550B1 (fr) | Dispositif adhésif pour application au tissu corporel | |
US5955097A (en) | Pharmaceutical preparation applicable to mucosal surfaces and body tissues | |
US5081157A (en) | Compositions and in situ methods for forming films on body tissue | |
US5688520A (en) | Transmucosal delivery of melatonin for prevention of migraine | |
EP0641192B1 (fr) | Dispositif d'apport de medicament a travers des muqueuses | |
US5081158A (en) | Compositions and in situ methods for forming films on body tissue | |
US6159498A (en) | Bioerodable film for delivery of pharmaceutical compounds of mucosal surfaces | |
Smart | Drug delivery using buccal-adhesive systems | |
CA1290695C (fr) | Composition pharmaceutique pour les parodontapathies | |
WO1996009829A1 (fr) | Ameliorations d'excipients pour application locale par voie muqueuse | |
JP2735392B2 (ja) | 乾癬の治療法 | |
JP3000104B2 (ja) | 身体組織上の本来の部位にフィルムを形成する組成物及び方法 | |
TR200100628T2 (tr) | Mukozaya yapışan (muko-adhesif) oral sıvı bileşimler. | |
TR200100569T2 (tr) | Mukozaya yapışan (muko-adhesif) oral sıvı bileşimler | |
JPS6270318A (ja) | 止血及び創傷保護剤 | |
TR200100566T2 (tr) | Mukozaya yapışan(muko-adhesif)oral sıvı bileşimler | |
JPH0214059B2 (fr) | ||
AU769500B2 (en) | Pharmaceutical carrier device suitable for delivery of pharmaceutical compounds to mucosal surfaces | |
JP3915027B2 (ja) | 口内炎用薬剤 | |
WO1995022983A1 (fr) | Composition topique pour le traitement des ulceres aphteux, contenant un agent anti-microbien et un corticosteroide | |
JP2697884B2 (ja) | 口腔内貼付用バンデージ | |
JPS62255417A (ja) | 口腔内製剤 | |
JPS6311942Y2 (fr) | ||
KR940000102A (ko) | 구내염 치료용 첩부제 | |
JPH0368672A (ja) | 粘着テープ |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA JP KR |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
122 | Ep: pct application non-entry in european phase | ||
NENP | Non-entry into the national phase |
Ref country code: CA |