Treatment of mucosal membranes

• US 7,087,249 B2
• Filed: 04/23/2002
• Issued: 08/08/2006
• Est. Priority Date: 04/23/2001
• Status: Expired due to Term

• Current Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Original Assignee: NUCRYST Pharmaceuticals Corp. (The Westaim Corporation)
• Inventors: Moxham, Peter Howard, Naylor, Antony George, Burrell, Robert Edward
• Primary Examiner(s): PAK, JOHN D
• Application Number:
  US10/131,509
• Publication Number:
  US 20030099718A1
• Time in Patent Office: 1,568 Days
• Field of Search: 424/400, 424/402, 424/404, 424/405, 424433-436, 424/443, 424/457, 424/458, 424/468, 424/469, 424/489, 424/490, 424617-619, 424/646, 424/649, 424/DIG.15, 514/184, 514/492, 514/495, 514/826, 514/849, 514/851, 514/853, 514/882, 514/886, 514/887, 514900-902, 514/912, 514/914, 514/925, 514931-934, 514/951, 514/953, 514/954, 514/956, 514/958, 514/964, 514965-969, 514/825
• US Class Current: 424/618
• CPC Class Codes: A01N 25/04 Dispersions, emulsions, suspoemulsions, suspension concentrates or gels foams A01N25/16
• CPC Class Codes: A01N 25/10 Macromolecular compounds
• CPC Class Codes: A01N 25/12 Powders or granules A01N25/26 takes precedence
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/242 Gold; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: A61K 33/40 Peroxides
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 17/145 Coating
• CPC Class Codes: A61L 2300/102 : Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
• CPC Class Codes: A61L 2300/104 : Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/404 : Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/452 : Lubricants
• CPC Class Codes: A61L 2300/606 : Coatings
• CPC Class Codes: A61L 2300/624 : Nanocapsules
• CPC Class Codes: A61L 2300/63 : Crystals
• CPC Class Codes: A61L 27/30 : Inorganic materials
• CPC Class Codes: A61L 29/10 : Inorganic materials
• CPC Class Codes: A61L 31/082 : Inorganic materials
• CPC Class Codes: A61P 1/00 : Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 : Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 : Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/04 : for throat disorders
• CPC Class Codes: A61P 13/00 : Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/08 : of the prostate
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 : Antipruritics
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/08 : Antiseborrheics
• CPC Class Codes: A61P 17/10 : Anti-acne agents
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/16 : Otologicals
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: Y10S 424/15 : Suppositories
• CPC Class Codes: Y10T 428/31855 : Of addition polymer from unsaturated monomers

Abstract

The invention relates to the use of one or more antimicrobial metals preferably selected from silver, gold, platinum, and palladium but most preferably silver, formed with atomic disorder, and preferably in a nanocrystalline form, for reducing inflammation or infection of the mucosal membrane. The antimicrobial metal may be formulated as, or used in the form of, a nanocrystalline coating of one or more antimicrobial or noble metals, a nanocrystalline powder of one or more antimicrobial or noble metals, or a liquid or solution containing dissolved species from a nanocrystalline powder or coating of one or more antimicrobial or noble metals.

Claims

1. A method of reducing inflammation or infection of a mucosal membrane, comprising:

contacting an inflamed or infected problem area of the mucosal membrane with a therapeutically effective amount of one or more antimicrobial metals in nanocrystalline form to provide a localized anti-inflammatory or antimicrobial effect, wherein the one or more antimicrobial metals are selected from the group consisting of silver, gold, platinum and palladium and characterized by sufficient atomic disorder so that the metal, in contact with an alcohol or water-based electrolyte, releases atoms, ions, molecules, or clusters of said metal on a sustainable basis and at a concentration sufficient to provide a localized anti-inflammatory or antimicrobial effect.

2. The method of claim 1, wherein the one or more antimicrobial metals provide a localized antimicrobial effect.

3. The method of claim 2, wherein the mucosal membrane is one or more of the oral cavity, the nasal, bronchial, pulmonary, trachea and pharynx airways, the otic and ophthalmic surfaces, the urogenital system, the reproductive system, and the gastrointestinal tract.

4. The method of claim 2, wherein the mucosal membrane is the oral cavity, the nasal, bronchial, pulmonary, trachea and pharynx airways, the urogenital system, the reproductive system, or the gastrointestinal tract.

5. The method of claim 2, wherein the mucosal membrane is the prostate, the colon or rectal surfaces.

6. The method of claim 1, wherein the antimicrobial metal is nanocrystalline silver.

7. The method of claim 1, wherein the antimicrobial metal is nanocrystalline silver, formed as a composite with oxygen.

8. The method of claim 1, wherein the antimicrobial metal is delivered as a powder, aerosol, spray, mist to the oral cavity, or to an area of the nasal, bronchial, pulmonary, trachea or pharynx airways to a respiratory disorder.

9. The method of claim 8, wherein the antimicrobial metal is nanocrystalline silver delivered as an aerosol, wherein the aerosol has a droplet size which is less than 10 μ

m, and wherein the concentration of silver in the aerosol is in the range of 40 to 500 μ

g/ml.

10. The method of claim 9, wherein the aerosol does not contain particulates sized larger than 2 μ

m.

11. The method of claim 10, wherein the aerosol does not contain particulates sized larger than 1 μ

m.

12. The method of claim 1, wherein the one or more antimicrobial metals are provided as a coating on, or filler in, a dressing, substrate or patch, or in a pharmaceutical composition with one or more pharmaceutically acceptable carriers suitable for application to the mucosal membrane.

13. The method of claim 12, wherein the pharmaceutical composition includes a nanocrystalline powder of the one or more antimicrobial metals, or a liquid containing dissolved species from a nanocrystalline powder or coating of the one or more antimicrobial metals.

14. The method of claim 13, wherein the pharmaceutical composition is a one or more of a gel, cream, lotion, paste, ointment, foam, suppository, lozenge, gum, tablet, capsule, or wafer containing the antimicrobial metal powder in an amount of 0.01-10% by weight, or one or more of a liquid formulated as a topical solution, aerosol, instillation, infusion, spray, mist, drops, syrup, elixir, mouth wash, or retention enema containing 0.001-10% by weight of the antimicrobial metal.

15. The method of claim 14, wherein the mucosal membrane is contacted to treat a respiratory disorder, a disease or condition of the oral cavity, a gastrointesinal disorder, a nasal disorder, or a disorder of the urogenital or reproductive system.

16. The method of claim 15, wherein the antimicrobial metal is nanocrystalline silver.

17. The method of claim 15, wherein the antimicrobial metal is silver, formed as a composite with oxygen.

18. The method of claim 12, wherein the dressing or pharmaceutical composition is fixed in place or occluded with an occlusive or semi-occlusive layer which maintains the dressing or composition in a moist condition.

19. The method of claim 12, wherein the one or more antimicrobial metals are provided in a hydrated or hydrocolloid-containing dressing, or in a pharmaceutical composition with one or more hydrocolloids.

20. The method of claim 19, wherein the hydrocolloid is one or more of cellulose and derivatives thereof, starch, glycogen, gelatin, pectin, alginate, chitosan, chitin, gum arabic, locust bean gum, karaya gum, gum tragacanth, ghatti gum, agar-agar, carrageenans, carob gum, guar gum, and xanthan gum.

21. The method of claim 20, wherein the hydrocolloid is one or more of carboxymethyl cellulose, alginate, pectin, and glyceryl polymethacrylate.

22. The method of claim 21, wherein the antimicrobial metal is nanocrystalline silver.

23. The method of claim 21, wherein the antimicrobial metal is nanocrystalline silver, formed as a composite with oxygen.

24. The method of claim 1, wherein the antimicrobial metal is in a powder form and is delivered directly to the mucosal membrane.

25. The method of claim 24, wherein the powder is sized with particulates no larger than 2 μ

m.

26. The method of claim 25, wherein the powder is sized with particulates no larger than 1 μ

m.

27. The method of claim 26, wherein the antimicrobial metal is nanocrystalline silver.

28. The method of claim 26, wherein the antimicrobial metal is nanocrystalline silver, formed as a composite with oxygen.