WO2011049960A2 - Compositions et méthodes pour le traitement des troubles nasosinusiens - Google Patents
Compositions et méthodes pour le traitement des troubles nasosinusiens Download PDFInfo
- Publication number
- WO2011049960A2 WO2011049960A2 PCT/US2010/053217 US2010053217W WO2011049960A2 WO 2011049960 A2 WO2011049960 A2 WO 2011049960A2 US 2010053217 W US2010053217 W US 2010053217W WO 2011049960 A2 WO2011049960 A2 WO 2011049960A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sinonasal
- composition
- formulation
- active agent
- nasal
- Prior art date
Links
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- 238000000034 method Methods 0.000 title claims abstract description 194
- 238000011282 treatment Methods 0.000 title claims abstract description 35
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- 239000013543 active substance Substances 0.000 claims abstract description 262
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- 239000012730 sustained-release form Substances 0.000 claims description 108
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
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- QJVHTELASVOWBE-AGNWQMPPSA-N (2s,5r,6r)-6-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 QJVHTELASVOWBE-AGNWQMPPSA-N 0.000 claims description 5
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—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
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- 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
- A61K9/0043—Nose
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the nasal cavity, sinonasal caity and nasopharynx form a functional unit.
- Humans have four pairs of sinusoidal cavities placed symmetrically on opposite sides of the head.
- the nasal cavity is divided into the olfactory region and respiratory region placed behind the nose in the middle of the face.
- the nasopharynx includes the respiratory passage above and behind the soft palate.Certain sinonasal, nasal, and nasopharynx conditions are associated with infection and/or inflammation and/or allergic response and/or deformities in sinonasal, nasal, and nasopharynx cavities or structures.
- Described herein are methods for providing sustained release of desired agents to, or in the vicinity of, at least one structure or region of the sinusoidal, nasal, and/or
- nasopharynx cavities, structures or passages are administered to, or in the vicinity of, the sinusoidal and/or nasal and/or nasopharynx regions.
- Administration of sustained release compositions and formulations described herein into, or in the vicinity of, the sinusoidal and/or nasal and/or nasopharynx regions allows for treatment of sinusoidal, nasal, and/or nasopharyngeal disorders, including, and not limited to, sinonasal polyposis, allergic fungal sinusitis, chronic sinusitis, reduction of post-surgical complications associated with sinonasal surgery (e.g., inferior turbinate removal, polypectomy), nasal polyps, and nasopharyngeal cancers.
- the methods of treatment described herein reduce recurrence of a sinonasal condition and/or complications after surgery for a sinonasal condition.
- the methods of treatment described herein reduce recurrence of a nasal condition (e.g., a polyp) and/or complications after surgery for a nasal condition.
- the methods of treatment described herein reduce the frequency of dose administration thereby increasing patient comfort and/or compliance.
- the sustained release formulations e.g., intrasinusoidal and/or nasal formulations
- the sustained release formulations described herein that are suitable for use in the methods described herein, comprise an anti-inflammatory agent, or an antibiotic, or an antifungal, or an antiviral, or a chemotherapeutic agent, or an antiangiogenesis agent, or a growth factor, or a combination thereof.
- the methods described herein comprise the use of sustained release intrasinusoidal and/or nasal and/or nasopharyngeal formulations in combination with surgical procedures such as sinoplasty, ballon rhinoplasty,
- kits for providing sustained release of an active agent into one or more sinonasal cavities of a human comprising administering to one or more sinonasal cavities, or in the vicinity of one or more sinonasal cavities of the human in need thereof a pharmaceutical composition comprising:
- composition provides sustained release of the one or more active agents into or in the vicinity of one or more sinonasal cavities for a period of at least 3 days.
- the composition provides sustained release of the one or more active agents into or in the vicinity of one or more sinonasal cavities for a period of at least 5 days. In some embodiments of the methods, the composition provides sustained release of the one or more active agents into or in the vicinity of one or more sinonasal cavities for a period of at least 7 days. In some embodiments of the methods, the composition provides sustained release of the one or more active agents into or in the vicinity of one or more sinonasal cavities for a period of at least 10 days. In some embodiments of the methods, the composition provides sustained release of the one or more active agents into or in the vicinity of one or more sinonasal cavities for a period of at least 14 days.
- the pharmaceutical composition is a thermoreversible gel.
- thermoreversible gel has a gelation temperature of less than about 42 °C. In some embodiments of the methods, the
- thermoreversible gel has a gelation temperature between about 5 °C and about 37 °C.
- the composition is a liquid at the time of administation and wherein the liquid is suitable for administration via a narrow gauge needle or cannula or catheter.
- the composition is administered as a nasal spray.
- the one or more active agents comprises multiparticulates.
- the one or more active agents is essentially in the form of micronized particles.
- the one or more active agents is a
- the amount of corticosteroid in the composition is between about 0.01 to about 25% by weight of the composition.
- the corticosteroid is 21 -acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, flupre
- the corticosteroid is dexamethasone, prednisolone, methylprednisolone, triamcinolone, or a salt or prodrug thereof, or a combination thereof. In some embodiments of the methods, the corticosteroid is
- the dexamethasone is dexamethasone sodium phosphate or dexamethasone acetate.
- the composition comprises multiparticulate corticosteroid. In some embodiments of the methods, the multiparticulate corticosteroid is essentially micronized corticosteroid.
- the composition provides an in vivo sustained release of a therapeutically effective amount of corticosteroid for a period of at least 5 days. In some embodiments of the methods, the composition provides an in vivo sustained release of a therapeutically effective amount of corticosteroid for a period of at least 7 days.
- the one or more active agents is an antimicrobial agent.
- the antimicrobial agent is an antibiotic.
- the amount of antibiotic in the first or more active agents is an antimicrobial agent.
- composition is between about 0.01 to about 20% by weight of the composition
- the antibiotic is amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin, paromycin, geldanamycin, herbimycin, loracarbef, ertapenem, doripenem, imipenem, meropenem, cefaclor, cefamandole, cefotoxin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefepime, ceftobirprole, vancomycin, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, spectinomycin, aztreonam, amoxicillin, ampicillin, azociling, carb
- the composition comprises multiparticulate antibiotic.
- the multiparticulate antibiotic is essentially micronized antibiotic.
- the antibiotic agent is ciprofloxacin, amoxicillin, amoxicillin+clavulanic acid, moxifloxacin or ofloxacin, or salt or solvate thereof. In some embodiments of the methods, the antibiotic agent is ciprofloxacin or ciprofloxacin hydrate.
- the composition provides an in vivo sustained release of a therapeutically effective amount of antibiotic agent for a period of at least 5 days. In some embodiments of the methods, the composition provides an in vivo sustained release of a therapeutically effective amount of antibiotic agent for a period of at least 7 days.
- the one or more active agents is a combination of a corticosteroid and an antibiotic.
- the composition is an aspetic mixture of sterile active agent and a sterile solution comprising a copolymer of polyoxy ethylene and polyoxypropylene.
- the composition comprises between about 14.0% and about 27% of a copolymer of polyoxyethylene and polyoxypropylene. In some embodiments of the methods, the composition comprises between about 14.5% and about 25% of a copolymer of polyoxyethylene and polyoxypropylene. In some embodiments of the methods, the composition comprises between about 14.5% and about 21% of a copolymer of polyoxyethylene and polyoxypropylene. In some embodiments of the methods, the composition comprises between about 15% and about 18% of a copolymer of polyoxyethylene and polyoxypropylene. In some of such embodiments, the formulation further comprises a viscosity enhancing agent as described herein. In some other embodiments of the methods, the composition comprises between about 25% and about 50% of a copolymer of polyoxyethylene and polyoxypropylene.
- the copolymer of polyoxyethylene and polyoxypropylene is Poloxamer 407 (also known as PF-127, Pol-407, Pluronic- 127).
- the composition further comprises a mucoadhesive.
- the composition has a pH of between about 3.0 and about 12.0. In some embodiments of the methods, the composition has a pH of between about 5.0 and about 9.0. In some embodiments of the methods, the composition has a pH of between about 7.0 and about 8.0.
- composition provides sustained release of the one or more active agents into or in the vicinity of one or more sinonasal cavities for a period of at least 3 days.
- the one or more active agents is selected from a corticosteroid, an antibiotic, or a combination thereof.
- the composition is administered in an ethmoid, maxillary, frontal or sphenoid sinusoidal cavity, or any combination thereof. In some embodiments of the methods described above, the composition is administered into a polyp. In some embodiments of the methods described above, the composition is administered in the vicinity of a polyp. In some embodiments of the methods described above, the composition is administered in a nasal cavity.
- compositions comprising
- composition provides sustained release of the one or more active agents into or in the vicinity of one or more sinonasal cavities for a period of at least 3 days.
- the one or more active agents is selected from a corticosteroid, an antibiotic, or a combination thereof.
- the surgery is inferior turbinate removal, or removal of sinonasal polyps or balloon rhinoplasty.
- the surgery is removal of polyps.
- the composition is administered at the site of the polyps after removal of the polyps.
- the method prevents or reduces recurrence of sinonasal polyps after surgical removal of the sinonasal polyps.
- a method for treatment of chronic sinusitis, sinonasal polyps, or allergic fungal sinusitis comprising administration in one or more sinonasal cavities, or in the vicinity of one or more sinonasal cavities, of an individual in need thereof a composition comprising comprising a thermoreversible polymer and a corticosteroid, wherein the composition provides sustained release of a corticosteroid into or in the vicinity of one or more sinonasal cavities for a period of at least 3 days, at least 5 days, or atleast 7 days.
- the composition further comprises an antimicrobial agent.
- the antimicrobial agent is an antibiotic.
- compositions comprising comprising a thermoreversible polymer and a corticosteroid, wherein the composition provides sustained release of a corticosteroid into or in the vicinity of one or more sinonasal cavities for a period of at least 3 days, at least 5 days, or at least 7 days.
- the composition further comprises an antimicrobial agent.
- the antimicrobial agent is an antibiotic.
- a method for treating sinonasal cancers comprising administration in one or more sinonasal cavities, or in the vicinity of one or more sinonasal cavities, of an individual in need thereof a composition comprising comprising a thermoreversible polymer and a corticosteroid, wherein the composition provides sustained release of a corticosteroid into or in the vicinity of one or more sinonasal cavities for a period of at least 3 days, at least 5 days or at least 7 days.
- the composition further comprises an antimicrobial agent.
- the antimicrobial agent is an antibiotic.
- a method for determination of release of an active agent from a sustained release sinonasal formulation in an individual in need thereof comprising analysis of nasal lavage or sinusoidal lavage of the individual and detecting the presence of active agent in the nasal lavage or sinusoidal lavage.
- the presence of an active agent in the nasal or sinusoidal lavage is determined using any suitable technique (e.g, UV spectrometry, HPLC, Mass Spectrometry or NMR analysis).
- tissue exposure of an active agent is determined using any suitable technique (e.g, UV spectrometry, HPLC, Mass Spectrometry or NMR analysis).
- any composition described above is substantially free of additional preservatives. In some embodiments, any composition described above is substantially free of additional tonicity agents. In some embodiments, any composition described above has any individual product related impurity of no more than 1%. In some embodiments, any composition described above has total product related impurities of no more than 2%.
- the dexamethasone, or salt or prodrug or solvate thereof is present in an amount from about 0.05% to about 40% by weight of the formulation. In some embodiments of any composition described above, the dexamethasone, or salt or prodrug or solvate thereof, is present in an amount from about 0.1% to about 30% by weight of the formulation. In some embodiments of any composition described above, the dexamethasone, or salt or prodrug or solvate thereof, is present in an amount from about 0.2% to about 20% by weight of the formulation.
- the ciprofloxacin, or salt or solvate thereof is present in an amount from about 0.05% to about 40% by weight of the formulation. In some embodiments of any composition described above, the ciprofloxacin, or salt or solvate thereof, is present in an amount from about 0.1% to about 30% by weight of the formulation. In some embodiments of any composition described above, the ciprofloxacin, or salt or solvate thereof, is present in an amount from about 0.2% to about 20% by weight of the formulation.
- Figure 1 is an illustrative comparison of non-sustained release and sustained release formulations.
- Figure 2 are illustrative predicted tunable releases of an agent from four compositions.
- Figure 3 is an illustration of in vitro mean dissolution time with increasing concentrations of steroid drug in sustained release formulations.
- Figure 4 is an illustration of in vitro mean dissolution time of high versus low solubility drug substances and solution versus gel formulations.
- Figure 5 illustrates the hemolysis in guinea pig red blood cells when exposed to serially diluted poloxamer solutions.
- sustained release instrasinusoidal, intranasal, and/or intranasopharyngeal compositions and formulations for the treatment of sinusoidal, nasal, and/or nasopharynx disorders including, and not limited to, sinonasal polyposis, allergic fungal sinusitis, nasal polyps, paranasal sinus cancers, nasopharyngeal cancers, epistaxis, anosmia, respiratory papilloma, inferior turbinate removal, reduction of post-surgical complications associated with sinonasal surgery, and chronic sinusitis or rhinosinusitis.
- kits for providing sustained release of an active agent into, or in the vicinity of, a sinonasal cavity of a human are also provided herein, in some embodiments, are methods for providing sustained release of an active agent into, or in the vicinity of, a nasal or nasopharyngeal region of a human.
- sustained release of an active agent into the sinusoidal cavity of a human are methods for providing sustained release of an active agent into the sinusoidal cavity of a human.
- intrasinusoidal formulations described herein are administered in the sinus cavity and/or in the vicinity of the sinus cavity.
- Current treatment regimens for sinusodial conditions include nasal sprays and/or nasal irrigation for topical drug administration into the paranasal sinuses.
- nasal sprays and/or nasal irrigation are not effective in delivering a solution in the paranasal sinuses and/or the sinusoidal cavities.
- the solutions drain out of the nasal passages.
- sustained release of active agents in the paranasal cavities comprising administration of sustained release formulations in a sinonasal cavity or in the vicinity of a sinonasal cavity of an individual in need thereof.
- the sustained release formulations described herein gel upon contact with sinonasal surfaces and adhere to surfaces in sinonasal cavities or to surfaces in the vicinity of sinonasal cavities thereby providing a depot for extended release of an active agent from an administered formulation.
- the methods and/or formulations described herein prolong residence time of an active agent in a sinonasal region or in the vicinity of a site of sinonasal inflammation and/or infection.
- nasal cavities There is also considerable anatomical variation in the nasal cavities amongst individuals.
- Current treatment regimens for nasal disorders include nasal sprays and/or nasal irrigation for topical drug administration into the nasal cavity.
- nasal sprays and/or nasal irrigation are not effective in retaining a medicament in a nasal cavity.
- nasal formulations that gel upon contact with a nasal surface.
- the sustained release nasal formulations described herein adhere to the surfaces of nasal regions and do not drain out of the nasal passages, thereby providing sustained release of an active agent in the affected region.
- sustained release of an active agent into the nasopharynx of a human are administered in the nasopharynx and/or in the vicinity of the nasopharynx and provide sustained release of an active agent in the affected region.
- the methods described herein comprise the use of sinusoidal and/or nasal and/or nasopharynx formulations that are manufactured with low bioburden or sterilized with stringent sterility requirements and are suitable for administration to the vulnerable environment in the sinonasal cavities.
- the compositions described herein are substantially free of pyrogens and/or microbes.
- a disadvantage of liquid formulations is their propensity to drain into nasal passages and cause rapid clearance of the formulation.
- methods for providing sustained release of active agents in sinonasal cavities comprising administration of fomulations that comprise thermoreversible polymers that gel at about body temperature and remain in contact with the target sinonasal surfaces for extended periods of time.
- Instrasinusoidal and/or nasi and/or nasopharyngeal formulations described herein avoid attenuation of therapeutic benefit due to drainage or leakage of active agents via the nasal passages.
- the methods described herein utilize intrasinusoidal and/or nasal and/or
- the compositions are formulated with minimum excipients and thus reduce or eliminate irritation or toxicity in the environment of sinonasal cavities or regions.
- the formulations comprise thermoreversible polymers that are biocompatible and/or otherwise non-toxic to the sinonasal environment.
- the thermoreversible gel is biodegradable and/or bioeliminated (e.g., the copolymer is eliminated from the body by a biodegradation process, e.g., elimination in the urine, the feces or the like).
- a formulation described herein comprises at least about 5.0% and not more than about 50% of a thermoreversible polymer (e.g., polyoxyethylene- polyoxypropylene triblock copolymer) by weight of the composition.
- a thermoreversible polymer e.g., polyoxyethylene- polyoxypropylene triblock copolymer
- a formulation described herein comprises at least about 5.0% and not more than about 40% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10.0% and not more than about 35% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10.0% and not more than about 30% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10.0% and not more than about 25% of a thermoreversible polymer (e.g., polyoxyethylene- polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments,
- a formulation described herein comprises at least about 12.0% and not more than about 25% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10% and not more than about 20% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 12% and not more than about 20% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition.
- a thermoreversible polymer e.g., polyoxyethylene-polyoxypropylene triblock copolymer
- thermoreversible polymer comprising polyoxyethylene and polyoxypropylene copolymers
- a formulation described herein comprises at least about 5% and not more than about 20% of a thermoreversible polymer (e.g., polyoxyethylene- polyoxypropylene triblock copolymer) by weight of the composition.
- a thermoreversible polymer e.g., polyoxyethylene- polyoxypropylene triblock copolymer
- a formulation described herein comprises at least about 10% and not more than about 20% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10% and not more than about 18% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10% and not more than about 16% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10% and not more than about 15% of a thermoreversible polymer (e.g., polyoxyethylene- polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments,
- a formulation described herein comprises at least about 12% and not more than about 14% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition. In some embodiments, a formulation described herein comprises at least about 10% and not more than about 13% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition.
- a thermoreversible polymer e.g., polyoxyethylene-polyoxypropylene triblock copolymer
- a formulation described herein comprises at least about 5 % and not more than about 15%, 16%, 17%, 18%, 19% or 20% of a thermoreversible polymer (e.g., polyoxyethylene-polyoxypropylene triblock copolymer) by weight of the composition.
- a thermoreversible polymer e.g., polyoxyethylene-polyoxypropylene triblock copolymer
- the thermoreversible polymer comprising polyoxyethylene-polyoxypropylene triblock copolymers is P407.
- a formulation described herein comprises at least about 5.0%, 10.0%, 10.5%, 1 1.0%, 1 1.5%, 12.0%, 12.5%, 13.0%, 13.5%, 14.0%, 14.5%, 15.0%, 15.5%, 16.0%, 16.5%, 17.0%, 17.5%, or 18.0% and not more than about 14.5%, 15.0%, 15.5%, 16.0%, 16.5%, 17.0%, 17.5%, 18.0%, 18.5%, 19.0%, 20.0%, 21.0%, 25.0%, 30%, 40% or 50% of P407 by weight of the composition.
- thermoreversible polymer comprising polyoxyethylene-polyoxypropylene triblock copolymers is purified P407. In some other embodiments, the thermoreversible polymer comprising polyoxyethylene-polyoxypropylene triblock copolymers is non-purified P407 (e.g., commercially purchased P407).
- formulations described above have a gelation temperature between about 5 °C and about 42 °C and comprise between about 5% to about 40% of a thermoreversible polymer by weight of the composition.
- formulations described above have a gelation temperature between about 14 °C and about 42 °C and comprise between about 5% to about 40% of a thermoreversible polymer by weight of the composition.
- the about 5% to about 40% of a thermoreversible polymer comprises a polyoxyethylene-polyoxypropylene triblock copolymer by weight of the composition.
- the thermoreversible polymer e.g., polyoxyethylene-polyoxypropylene triblock copolymer
- the thermoreversible polymer is purified.
- the thermoreversible polymer e.g., polyoxyethylene-polyoxypropylene triblock copolymer
- is un-purified e.g., commercially available P407 NF from BASF.
- the about 5% to about 40% of a thermoreversible polymer comprises a polyoxyethylene-polyoxypropylene triblock copolymer and the formulation further comprises a gel temperature modulating agent.
- a gel temperature modulating agent is selected from, for example, cyclodextrin, PEG, PI 88, P338, carboxymethyl cellulose, hyaluronic acid, Carbopol®, chitosan, or the like.
- the formulations comprise purified poloxamer.
- a formulation comprising a purified poloxamer contains a lower poloxamer concentration compared to a formulation comprising non-purified poloxamer while retaining the ability to gel at a temperature between about 5 °C and about 42 °C.
- a formulation comprising a purified poloxamer contains a lower poloxamer concentration compared to a formulation comprising non- purified poloxamer while retaining the ability to gel at a temperature between about 14 °C and about 42 °C.
- a micronized dexamethasone formulation comprising between about 10% and about 12% of fractionated poloxamer 407 gels at a temperature between about 14 °C and about 42 °C
- a micronized dexamethasone formulation comprising between about 14.5% and about 25% of un-purified poloxamer 407 also gels at a temperature between about 14 °C and about 42 °C.
- purified poloxamer allows for use of a lower amount of the thermoreversible polymer while retaining the gel temperature and sustained release properties of the formulation.
- active compositions comprising primarily a thermoreversible polymer comprising poly oxy ethylene and polyoxy ethylene copolymers as a major component polymer and a gel temperature modifying agent as a minor component polymer such that the formulation retains the ability to gel at temperatures between about 5 °C and about 42 °C, or between about 14 °C and about 42 °C.
- a composition comprising about 30% of non-purified P407 by weight of the composition, and about 3% PI 88 by weight of the composition gels at about body temperature.
- the intrasinusoidal and/or nasal and/or nasopharyngeal compositions described herein have a syringable visosity that allows for efficient administration in a clinical setting.
- a "syringable viscosity" is a viscosity that is low enough such that a pharmaceutical formulation described herein is a liquid that is capable of being
- a narrow gauge needle or cannula or catheter using normal finger pressure (e.g., by a physician using normal finger pressure on the plunger of the syringe, such that the needle of the syringe can accurately and stably deliver the
- formulations described herein are dispensed through a 18-31 gauge needle or cannula or catheter. In some embodiments, formulations described herein are dispensed through a 20-26 gauge needle or cannula or catheter. In some embodiments, formulations described herein are dispensed through a 25-31 gauge needle or cannula or catheter. In some embodiments, formulations described herein are dispensed through a 27- 31 gauge needle or cannula or catheter. In some embodiments, formulations described herein are syringable through a 27 gauge needle or cannula or catheter. In some
- formulations described herein are syringable through a 29 gauge needle or cannula or catheter. In some embodiments, formulations described herein are syringable through a 31 gauge needle or cannula or catheter.
- the formulations described herein are free or substantially free of additional thickening agents.
- additional thickening agents include chitosan, or polyethylene glycol (PEG).
- a formulation disclosed herein comprises less than about 5% by weight of chitosan.
- a formulation disclosed herein comprises less than about 4% by weight of chitosan.
- a formulation disclosed herein comprises less than about 3% by weight of chitosan.
- a formulation disclosed herein comprises less than about 2% by weight of chitosan.
- a formulation disclosed herein comprises less than about 1% by weight of chitosan.
- a formulation disclosed herein comprises less than about 0.5% by weight of chitosan.
- the formulations described herein are free or substantially free of additional preservatives and are suitable for administration in sinonasal cavities and/or nasopharyngeal sites.
- Additional preservatives do not include trace amounts of antioxidants (e.g., Butylated hydroxytoluene (BHT)) that stabilize thermoreversible polymers, and which are typically provided commercially with thermoreversible polymers.
- antioxidants e.g., Butylated hydroxytoluene (BHT)
- BHT Butylated hydroxytoluene
- additional preservatives include benzethonium chloride, benzalkonium chloride, and thiomersal.
- a formulation disclosed herein comprises less than about 50 ppm of each of benzethonium chloride, benzalkonium chloride, and thiomersal.
- a formulation disclosed herein comprises less than about 25 ppm of each of benzethonium chloride, benzalkonium chloride, and thiomersal. In some embodiments, a formulation disclosed herein comprises less than about 20 ppm of each of benzethonium chloride, benzalkonium chloride, and thiomersal. In some embodiments, a formulation disclosed herein comprises less than about 10 ppm of each of benzethonium chloride, benzalkonium chloride, and thiomersal. In some embodiments, a formulation disclosed herein comprises less than about 5 ppm of each of benzethonium chloride, benzalkonium chloride, and thiomersal. In some embodiments, a formulation disclosed herein comprises less than about 1 ppm of each of benzethonium chloride, benzalkonium chloride, and thiomersal.
- the formulations described herein are free or substantially free of additional tonicity agents and are suitable for administration in the sinonasal cavities and/or nasopharyngeal sites.
- additional tonicity agents include propylene glycol.
- a formulation described herein is free or substantially free of propylene glycol.
- a formulation disclosed herein comprises less than about 50 ppm of propylene glycol.
- a formulation disclosed herein comprises less than about 25 ppm of propylene glycol.
- a formulation disclosed herein comprises less than about 20 ppm of propylene glycol.
- a formulation disclosed herein comprises less than about 10 ppm of propylene glycol. In some embodiments, a formulation disclosed herein comprises less than about 5 ppm of propylene glycol. In some embodiments, a formulation disclosed herein comprises less than about 1 ppm of propylene glycol. [0068] In some embodiments, the formulations described herein are free or substantially free of additional moisture retention agents and are suitable for administration in sinonasal sites. Examples of moisture retention agents include glycerin. Thus, in some embodiments, a formulation described herein is free or substantially free of glycerin. In some
- a formulation disclosed herein comprises less than about 50 ppm of glycerin. In some embodiments, a formulation disclosed herein comprises less than about 25 ppm of glycerin. In some embodiments, a formulation disclosed herein comprises less than about 20 ppm of glycerin. In some embodiments, a formulation disclosed herein comprises less than about 10 ppm of glycerin. In some embodiments, a formulation disclosed herein comprises less than about 5 ppm of glycerin. In some embodiments, a formulation disclosed herein comprises less than about 1 ppm of glycerin.
- the formulations described herein are substantially free of degradation products of the active agent and/or the polymer components.
- substantially free of degradation products means less than 5% by weight of the active agent and/or the polymer components are degradation products of the active agent and/or the polymer components.
- the term means less than 3% by weight of the active agent and/or the polymer components are degradation products of the active agent and/or the polymer components.
- the term means less than 2% by weight of the active agent and/or the polymer components are degradation products of the active agent and/or the polymer components.
- the term means less than 1% by weight of the active agent and/or the polymer components are degradation products of the active agent and/or the polymer components.
- the formulations described herein are free or substantially free of additional common solvents and are suitable for administration in sinonasal sites.
- additional solvents include ethanol, propylene glycol, DMSO, N-Methyl-2- pyrrolidone, and cyclohexane.
- a formulation described herein is free or substantially free of ethanol, propylene glycol, DMSO, N-Methyl-2-pyrrolidone, and cyclohexane.
- a formulation disclosed herein comprises less than about 50 ppm of each of ethanol, propylene glycol, DMSO, N-Methyl-2-pyrrolidone, and cyclohexane. In some embodiments, a formulation disclosed herein comprises less than about 25 ppm of each of ethanol, propylene glycol, DMSO, N-Methyl-2-pyrrolidone, and cyclohexane. In some embodiments, a formulation disclosed herein comprises less than about 20 ppm of each of ethanol, propylene glycol, DMSO, N-Methyl-2-pyrrolidone, and cyclohexane.
- a formulation disclosed herein comprises less than about 10 ppm of each of ethanol, propylene glycol, DMSO, N-Methyl-2-pyrrolidone, and cyclohexane. In some embodiments, a formulation disclosed herein comprises less than about 5 ppm of each of ethanol, propylene glycol, DMSO, N-Methyl-2-pyrrolidone, and cyclohexane. In some embodiments, a formulation disclosed herein comprises less than about 1 ppm of each of ethanol, propylene glycol, DMSO, N-Methyl-2-pyrrolidone, and cyclohexane.
- the formulations described herein are free or substantially free of additional antiseptics that are commonly used to disinfect any component of a sinonasal preparation and that are potentially toxic.
- additional antiseptics that are known to be toxic include acetic acid, iodine and merbromin.
- a formulation disclosed herein is free or substantially free of acetic acid, iodine, merbromin, and chlorhexidene.
- a formulation disclosed herein comprises less than about 50 ppm of each of acetic acid, iodine, merbromin, and chlorhexidene.
- a formulation disclosed herein comprises less than about 25 ppm of each of acetic acid, iodine, merbromin, and chlorhexidene.
- a formulation disclosed herein comprises less than about 20 ppm of each of acetic acid, iodine, merbromin, and chlorhexidene. In some embodiments, a formulation disclosed herein comprises less than about 10 ppm of each of acetic acid, iodine, merbromin, and chlorhexidene. In some embodiments, a formulation disclosed herein comprises less than about 5 ppm of each of acetic acid, iodine, merbromin, and chlorhexidene. In some embodiments, a formulation disclosed herein comprises less than about 1 ppm of each of acetic acid, iodine, merbromin, and chlorhexidene.
- intrasinusoidal preparations require particularly low concentrations of several potentially-common contaminants that are known to be toxic. Other dosage forms, while seeking to limit the contamination attributable to these compounds, do not require the stringent precautions that intrasinusoidal preparations require.
- the formulations described herein are free or substantially free of contaminants such as arsenic, lead, mercury, and tin.
- a formulation disclosed herein is free or substantially free of arsenic, lead, mercury, and tin.
- a formulation disclosed herein comprises less than about 50 ppm of each of arsenic, lead, mercury, and tin.
- a formulation disclosed herein comprises less than about 25 ppm of each of arsenic, lead, mercury, and tin. In some embodiments, a formulation disclosed herein comprises less than about 20 ppm of each of arsenic, lead, mercury, and tin. In some embodiments, a formulation disclosed herein comprises less than about 10 ppm of each of arsenic, lead, mercury, and tin. In some embodiments, a formulation disclosed herein comprises less than about 5 ppm of each of arsenic, lead, mercury, and tin. In some embodiments, a formulation disclosed herein comprises less than about 1 ppm of each of arsenic, lead, mercury, and tin.
- active agent pharmaceutical compositions or formulations disclosed herein are optionally targeted to distinct regions of the targeted sinonasal cavities, including but not limited to the ethmoid, maxillary, frontal and/or sphenoid sinusoidal cavities and other anatomical or physiological structures located within the sinonasal cavities such as nasal cavities, nasal polyps, turbinates, site of surgical wound or the like.
- amelioration or lessening of the symptoms of a particular sinonasal disease, disorder or condition by administration of a particular compound or pharmaceutical composition refers to any decrease of severity, delay in onset, slowing of progression, or shortening of duration, whether permanent or temporary, lasting or transient that is attributed to or associated with administration of the compound or composition.
- thermosetting polymers are polymers that undergo a reversible temperature-dependent phase transtion (e.g., a liquid to gel transition, a gel to liquid transition, or the like).
- thermoreversible polymers that form thermoreversible gels include and are not limited to poloxamers (e.g., Pluronics F68 R , F88 R , and F 108 ® , F127 ® , or the like) or any other thermosetting polymer described herein.
- Viscosity enhancing polymers are polymers that increase viscosity of a formulation described herein so that the formulation forms a thickened liquid upon administration.
- a viscosity enhanging polymer is a thermosensitive polymer.
- a thermosensitive polymer is not a thermoreversible polymer.
- a thermosensitive polymer is a thermoreversible polymer.
- Suitable viscosity-enhancing polymers that are thermosensitive polymers include and are not limited to, hydrogels (e.g., chitosan), gelatin, hyaluronic acid, acrylic acid based polymers (e.g., Carbopol®), MedGel®, cellulose based polymers (e.g.,
- the resulting formulation is a thermoreversible gel, but it need not be thermoreversible; that is, depending on the amount of thermosensitive polymer in the formulation, the resulting gel may be thermoreversible or not thermoreversible.
- a "purified" polymer is a commercially purchased polymer that is subjected to further steps prior to preparation of formulations described herein.
- a purified polymer has lower polydispersity (i.e., a narrower distribution of molecular weights amongst the individual polymer chains therein) and/or lower ethylene content and/or less unsaturation and/or weight% oxyethylene values compared to a commercially available sample of the same polymer.
- Purification is carried out using any suitable technique including and not limited to fractionation, chromatography, washing and/or decantation, purification using supercritical fluid (See, for example, U.S. Patent Appl. Pub. No.
- a purified poloxamer 407 is a fractionated P407 having a lower polydispersity index compared to a commercially purchased batch of P407 grade NF from BASF.
- the commercially purchased P407 has a polydispersity index of about 1.2.
- the polydispersity index of fractionated P407 as described herein is between about 1 and about 1.15.
- the polydispersity index of fractionated P407 as described herein is between about 1 and about 1.1.
- the polydispersity index of fractionated P407 as described herein is between about 1 and about 1.05.
- the calculated polydispersity index is the weight average molecular weight divided by the number average molecular weight of polymeric chains (M w /M n ). It indicates the distribution of individual molecular masses in a batch of polymers.
- an “effective amount” or “therapeutically effective amount,” as used herein, refer to a sufficient amount of the active agent or active agent (e.g., a corticosteroid agent, an antimicrobial agent, an anti-inflammatory agent or the like) being administered that would be expected to relieve to some extent one or more of the symptoms of the disease or condition being treated.
- the result of administration of an active agent disclosed herein is reduction and/or alleviation of the signs, symptoms, or causes of obstruction of ostea.
- an “effective amount” for therapeutic uses is the amount of active agent, including a formulation as disclosed herein required to provide a decrease or amelioration in disease symptoms without undue adverse side effects.
- “therapeutically effective amount” includes, for example, a prophylactically effective amount.
- An “effective amount” of an active agent disclosed herein is an amount effective to achieve a desired pharmacologic effect or therapeutic improvement without undue adverse side effects. It is understood that “an effective amount” or “a therapeutically effective amount” varies, in some embodiments, from subject to subject, due to variation in metabolism of the compound administered, age, weight, general condition of the subject, the condition being treated, the severity of the condition being treated, and the judgment of the prescribing physician. It is also understood that "an effective amount” in an extended- release dosing format may differ from “an effective amount” in an immediate release dosign format based upon pharmacokinetic and pharmacodynamic considerations.
- active agent refers to active agents that treat, or reduce or ameliorate severity of any sinonasal disorder described herein.
- Suitable “active agents” may be, for example, antimicrobial agents (e.g., antibacterial agents (effective against bacteria), antiviral agents (effective against viruses), antifungal agents (effective against fungal infections), corticosteroids, or any other active agent described herein.
- active agents may work by any suitable mechanism, including by being anti-inflammatory, antimicrobial, toxic, cytostatic and/or immunomodulatory agents.
- a sinonasal cavity refers to any cavity or passage or structure in the paranasal sinuses, or the nasal region.
- a sinonasal cavity is a maxillary, frontal, ethmoid or sphenoid sinus cavity.
- a sinonsasal cavity is in the nose or the vicinity of the nose or a nasal passage.
- a sinonasal cavity is in the nasopharynx region.
- the mean residence time is the average time that molecules of an active agent reside in a sinonasal structure after administration of a dose.
- a prodrug refers to an active agent that is converted into the parent drug in vivo.
- a prodrug is enzymatically metabolized by one or more steps or processes to the biologically, pharmaceutically or therapeutically active form of the compound.
- a pharmaceutically active compound is modified such that the active compound will be regenerated upon in vivo administration.
- the prodrug is designed to alter the metabolic stability or the transport characteristics of a drug, to mask side effects or toxicity, or to alter other characteristics or properties of a drug.
- Compounds provided herein, in some embodiments, are derivatized into suitable prodrugs.
- the term "subject” is used to mean an animal, preferably a mammal, including a human or non-human.
- the terms patient and subject may be used
- treat include alleviating, abating or ameliorating a disease or condition, for example sinusitis, symptoms, preventing additional symptoms, ameliorating or preventing the underlying metabolic causes of symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and/or therapeutically.
- Sinuses are paired air cavities/spaces (pockets) found in the cranial (head) bones. Sinuses are also referred to as "paranasal sinuses". They are connected to the nose on the facial part of the skull where air passes and mucus drains. Each sinus cavity has an opening (ostium), which opens into the nasal passages for free exchange of air and mucus. Each sinusoidal cavity is lined with a mucous membrane composed of ciliated epithelial cells that produce mucus and move dirty mucus out of the sinus cavities. Incoming particles of dirt are trapped by the mucus and moved by the cilia into the nasal cavity through small sinus openings called the ostia. A swelling of the mucus membranes causes blockage of the ostia. Blockage of normal sinus drainage leads to sinus inflammation and infection (sinusitis).
- Ethmoid (between the eyes) sinuses are located behind the bridge of the nose and at the "root" of the nose between the eyes.
- Frontal (forehead) sinuses are located above the eyes in the region of the forehead.
- Maxillary (cheekbones) sinuses are found on either side of the nostrils in the cheek bones.
- Sphenoid (behind the eyes) sinuses lie deeper in the skull behind the ethmoid sinuses and the eyes.
- the sinonasal cavities are an anatomically complex region; drainage of secretions from the sinusal cavities occurs through narrow passages including the ostiomeatal complex and the sphenoethmoid recess.
- the ostiomeatal unit is a final common pathway for drainage and ventilation of the frontal and maxillary sinuses and the anterior ethmoidal cells.
- the ethmoid infundibulum, middle nasal meatus, ethmoid bulla and frontal recess are included in the ostiomeatal complex.
- the sphenoethmoid recess is a bilateral slit-like recess high and posterior in the nasal cavity, between the anterior wall of the sphenoid sinus, the medial wall of the posterior ethmoid cells, and the posterosuperior part of the nasal septum.
- the sphenoid sinus and posterior ethmoid cells drain into the sphenoethmoid recess. In some instances, obstruction of these recesses and/or ostia lead to a disturbance in the mucociliary clearance of the dependent sinuses and induce sinusal inflammation.
- Anatomical variation in sinonasal cavities can result in sinusoidal disease.
- bony structure displacement such as nasal septum deviation causes perforation of the uncinate process.
- Nasal septum deviation may cause obstruction at the ostiomeatal unit and/or inflammation in the contralateral maxillary and ethmoidal sinuses.
- a paradoxically curved middle turbinate causes supplementary ostium in maxillary sinus.
- a supplementary ostium is a secondary opening between the maxillary sinus and the middle nasal meatus, most often found in the posterior nasal fontanelle.
- the supplementary ostium lies behind and below the natural ostium of the maxillary sinus, it predisposes certain individuals to sinusitis by recirculation ('recycling') of infected secretions from the nose back to the maxillary sinus.
- the nasal cavity is a fluid filled cavity/space found behind the nose where air passes on the way to the throat.
- the nasal cavity bony surfaces are lined by tissue called mucosa.
- This mucosa contains blood vessels, nerves, and small glands that secrete fluids into the nasal cavity.
- the mucosa supports cilia, which carry the mucous blanket from the front of the nose to the back.
- the nasal cavity is divided into the olfactory region and respiratory region with nasal chambers on either side of the median plane formed by the nasal septum.
- the respiratory region is lined with respiratory epithelium.
- the olfactory segment is lined with olfactory epitheulium which contains receptors for the sense of smell.
- Olfactory mucosal cell types include: bipolar neurons, supporting cells, basal cells and Bowman's glands. Anosmia is a nasal condition that causes the loss of smell.
- the nose Because of its prominent position, the nose is especially vulnerable to injury, including fractures. Infections, nose bleeds (epistaxis), and polyps also can affect the nose. The mucous membrane of the nose may become inflamed (rhinitis). Nasal cancers occur when malignant cells form in the tissues of the nasal cavity, e.g., B cell lymphomas.
- the nasopharynx is the upper portion of the pharynx (the tube at the back of the throat), and it lies just above the soft palate in the mouth.
- the nasopharynx is an important passageway that allows air to travel from the nose into the windpipe (trachea) and food into the foodpipe (esophagus).
- Located on the back wall of the nasopharynx are the pharyngeal tonsils, also called the adenoids, which are a network of immune system cells that defend the mucus membranes of the mouth and airways.
- the nasopharynx also plays a role in hearing because openings at the side of pharynx connect the hearing tube to each ear.
- Sinonasal conditions include, and are not limited to, chronic sinusitis, allergic fungal sinusitis, sinonasal polyposis, inferior turbinate removal, and/or any inflammation, swelling, infection, sinusoidal fullnes and congestion, inverted papillomas, recurrent respiratory papillomas, cancers of the nasopharynx, anosmia, epistaxis and the like.
- Chronic sinusitis or chronic rhinos inusitis (CRS) is an inflammation and/or infection of the mucosa of the nose and/or paranasal sinuses and/or membranes lining the sinonasal cavities. This interferes with drainage and causes mucus buildup.
- Chronic sinusitis may be caused by an infection but can also be caused by growths in the sinuses (nasal polyps) or a deviated nasal septum. Sinusitis that lasts more than eight weeks or keeps coming back is classified as chronic sinusitis. Symptoms of chronic sinusitis include difficulty in breathing through the nose, swelling in the area around eyes and face, throbbing facial pain or a headache.
- kits for treating chronic or acute sinusitis comprising providing sustained release of active agents (e.g., corticosteroids, antimicrobial agents) in the sinonasal cavities.
- providing sustained release of active agents in the sinonasal cavities or in the vicinity of sinonasal cavities comprises administration of a pharmaceutical composition comprising a thermoreversible polymer and a corticosteroid, wherein the composition gels at a temperature between about the temperature of administration and about the physiological body temperature of an individual.
- methods of treating chronic or acute sinusitis comprise providing sustained release of active agents (e.g., corticosteroids, antimicrobial agents) in or on a nasal polyp or in the vicinity of a nasal polyp.
- Nasal polyps are teardrop-shaped, noncancerous growths on the lining of nasal passages or sinuses. Larger nasal polyps can block nasal passages or sinuses and cause breathing difficulties, and/or frequent sinus infections. Children with cystic fibrosis often develop nasal polyps. In some cases, medication lessens the size of nasal polyps and/or eliminates them. But surgery is sometimes necessary to remove them. Small or isolated polyps are removed in a polypectomy using a small mechanical suction device or a microdebrider. Larger polyps are removed using endoscopic sinus surgery. The surgeon inserts an endoscope into sinus cavities and removes polyps and other obstructions that prevent the drainage of fluids from sinuses.
- corticosteroid nasal sprays are prescribed to prevent recurrence of polyps.
- the benefits are temporary and nasal polyps often recur.
- Nasal sprays and/or nasal irrigation are not effective in delivering a solution in the paranasal sinuses and/or the sinusoidal cavities.
- the solutions drain out of the nasal passages.
- providing sustained release of active agents in or on the polyps and/or in the vicinity of the polyps comprises administration of a pharmaceutical composition comprising a thermoreversible polymer and an active agent (e.g., a corticosteroid), wherein the composition gels at a temperature between about the temperature of administration and about the physiological body temperature of an individual.
- active agents e.g., corticosteroids, antimicrobial agents
- providing sustained release of active agents in or on the polyps and/or in the vicinity of the polyps comprises administration of a pharmaceutical composition comprising a thermoreversible polymer and an active agent (e.g., a corticosteroid), wherein the composition gels at a temperature between about the temperature of administration and about the physiological body temperature of an individual.
- the sinonasal compositions described herein are administered in combination with surgery for nasal polyps (e.g., polypectomy).
- a sinonasal composition is administered before surgery for nasal polyps.
- a sinonasal composition is administered during surgery for nasal polyps.
- a sinonasal composition is administered after surgery for nasal polyps.
- methods of treating nasal polyposis described herein prevent or reduce post-surgical complications (e.g., incidence of inflammation and/or infection after surgery, or recurrence of polyps after surgery).
- a sinonasal formulation is administered at the base of a polyp.
- a sinonasal formulation is administered at the site of a polyp after the polyp is removed.
- Allergic fungal sinusitis is believed to represent an immune-mediated, allergic-type response to environmental fungi that are dispersed in the air. This condition results in thick fungal debris and sticky mucus that must be surgically removed in order to keep the inflammatory condition under control. There is extensive nasal polyposis and fungal debris can expand and erode towards the eyes or brain. Surgeons endoscopically remove polyps and fungal debris that are adjacent to the skull base and eye while preserving normal structures, such as the septum and middle turbinate. Medical treatment consists of oral (prednisone) and topical steroids and immunotherapy (allergy shots). In spite of aggressive treatment, recurrence is not uncommon. In some embodiments, the methods described herein reduce or prevent allergic -type immune response in the sinuses and/or reduce recurrence of AFS. Sinonasal urgery
- the turbinates are long narrow curled bone shelves that divide the nasal airway into three groove-like air passages.
- Turbinates are composed of pseudostratified columnar, ciliated respiratory epithelium with a thick, vascular and erectile glandular tissue layer. The turbinates are located in pairs laterally in the nasal cavities, and are divided by the nasal septum.
- the inferior turbinates are the largest turbinates, and direct the majority of airflow direction, humidification, heating, and filtering of air inhaled through the nose.
- the middle turbinates are smaller and project downwards over the openings of the maxillary and ethmoid sinuses.
- the middle turbinates protect the sinuses from coming in direct contact with pressurized nasal airflow.
- the superior turbinates are the smallest structures and serve to protect the olfactory bulb.
- turbinate surgery is often required.
- Somnoplasty bipolar radiofrequency ablation
- reduction by the use of pure heat is used in turbinate sectioning.
- kits that comprise administration of sinonasal compositions described herein in the sinonasal cavities before, during and/or after surgery for sectioning and/or repositioning of swollen and/or otherwise deformed turbinates.
- the sinonasal compositions described herein are administered in combination with sinonasal surgery (e.g., inferior turbinate removal).
- a sinonasal composition is administered before sinonasal surgery (e.g., inferior turbinate removal).
- a sinonasal composition is administered during sinonasal surgery (e.g., inferior turbinate removal).
- a sinonasal composition is administered after sinonasal surgery (e.g., inferior turbinate removal).
- methods of treating sinonasal conditions described herein prevent or reduce post-surgical complications (e.g., incidence of inflammation and/or infection after surgery).
- methods described herein reduce and/or prevent recurrence of turbinate swelling after surgery and/or reduce post-surgical complications such as inflammation and/or infection.
- the different types of cells in the paranasal sinus, nasal cavity and nasopharynx may become malignant. Symptoms that may appear as the tumor grows include sinus pressure, a lump or sore inside the nose, numbness in the face, and pain in the teeth, ear, and/or eyes. Cancers of the paranasal sinus, nasal cavity and nasopharynx include but are not limited to squamous cell carcinoma, melanoma, sarcoma, inverting papilloma, recurrent respiratory papillomas, midline granulomas, and nasopharyngeal carcinomas. Papilloma virus induced tumors may be cancerous.
- sustained release formulations comprising antiviral agents (e.g., cidofovoir) for the treatment of virus indeed papillomas.
- antiviral agents e.g., cidofovoir
- Epstein Barr virus is associated with nasopharynx tumors.
- contemplated within the scope of compositions described herein is the use of sustained release sinonasal and/or
- nasopharyngeal compositions e.g., compositions comprising anticancer agents such as, and not limited to, gemcitabine, doxorubicin, ganciclovir, and the like
- anticancer agents such as, and not limited to, gemcitabine, doxorubicin, ganciclovir, and the like
- Wegener's granulomatosis is a form of autoimmune vasculitis (inflammation of blood vessels) that requires long-term immunosuppression.
- symptoms include pain, stuffiness, nosebleeds, rhinitis, crusting, or saddle-nose deformity due to a perforated septum.
- the methods of treatment and formulations provided herein advantageously reduce the frequency of dose administration during long term therapy of Wegener's granulomatosis.
- compositions described herein contemplated within the scope of compositions described herein is the use of sustained release sinonasal and/or nasopharyngeal compositions (e.g., compositions comprising agents such as, and not limited to, cyclophosphamide and the like) for the treatment of Wegener's granulomatosis.
- sustained release sinonasal and/or nasopharyngeal compositions e.g., compositions comprising agents such as, and not limited to, cyclophosphamide and the like
- Epistaxis is the occurrence of hemorrhage from the nose. Contemplated within the scope of embodiments presented herein is the use of sustained release formulations (e.g., formulations comprising antiangiogenic agents) for treatment of expistaxis.
- sustained release formulations e.g., formulations comprising antiangiogenic agents
- Anosmia is a temporary or permanent loss of ability to perceive odors.
- active agent compositions and formulations that treat sinonasal disorders and/or their attendant symptoms, including but not limited to sinonasal polyposis, allergic fungal sinusitis, chronic sinusitis, paranasal sinus cancers, nasopharyngeal cancers, Wegener's granulomatosis, epistaxis, anosmia, repiratory papillomas, congestion and/or reduce or prevent post-surgical complications associated with sinonasal surgery (e.g., inferior turbinate removal, polypectomy).
- sinonasal polyposis e.g., allergic fungal sinusitis, chronic sinusitis, paranasal sinus cancers, nasopharyngeal cancers, Wegener's granulomatosis, epistaxis, anosmia, repiratory papillomas, congestion and/or reduce or prevent post-surgical complications associated with sinonasal surgery (e.g., inferior turbinate removal, polyp
- any active agent useful for the treatment of intrasinusoidal, nasal or nasopharyngeal disorders e.g., inflammatory diseases and/or infections and/or deformities of the sinonasal and/or nasopharyngeal structures
- the active agent is an antimicrobial agent including an antibacterial agent, an antifungal agent, an antiviral agent, an antiprotozoal agent, and/or an antiparasitic agent.
- the active agent is a protein, a peptide, an antibody, DNA, an siRNA, a carbohydrate, an inorganic molecule, or an organic molecule. In certain embodiments, the active agents are antimicrobial small molecules.
- the active agent in a composition described herein is an antibacterial agent.
- the antibacterial agent treats infections caused by gram positive bacteria.
- the antibacterial agent treats infections caused by gram negative bacteria.
- the antibacterial agent treats infections caused by mycobacteria.
- the antibacterial agent treats infections caused by giardia.
- the antibacterial agent treats infections by inhibiting bacterial protein synthesis. In some embodiments, the antibacterial agent treats infections by disrupting synthesis of bacterial cell wall. In some embodiments, the antibacterial agent treats infections by changing permeability of bacterial cell membranes. In some
- the antibacterial agent treats infections by disrupting DNA replication in bacteria.
- the antibacterial agent is an antibiotic.
- the antibiotic is an aminoglycoside.
- aminoglycoside antibiotics include and are not limited to amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin, paromycin or the like.
- the antibiotic is an ansamycin. Examples of ansamycins include and are not limited to geldanamycin, herbimycin or the like.
- the antibiotic is a carbacephem. Examples of carbecephems include and are not limited to loracarbef or the like.
- the antibiotic is a carbapenem.
- the antibiotic is a cephalosporin (including, for example, first, second, third, fourth or fifth generation cephalosporins).
- cephalosporins include and are not limited to cefaclor, cefamandole, cefotoxin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefepime, ceftobirprole or the like.
- the antibiotic is a glycopeptide. Examples of glycopeptides include and are not limited to vancomycin or the like.
- the antibiotic is a macrolide antibiotic. Examples of macrolides include and are not limited to
- the antibiotic is a monobactam.
- monobactams include and are not limited to aztreonam or the like.
- the antibiotic is a beta-lactamase inhibitor and/or penicillin. Examples of beta-lactamase inhibitors include clavulanic acid and/or pencillins and/or beta- lactams.
- penicillins include and are not limited to amoxicillin, ampicillin, azociling, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, meticillin, nafcillin, oxacillin, peperacillin, ticarcillin, amoxcillin+ clavulanic acid (Augmentin®), or the like.
- the antibiotic is a quinolone.
- quinolones include and are not limited to ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nonfloxacin, ofloxacin, trovafloxacin, grepafloxacin, sparfloxacin, AL-15469A, AL-38905 or the like.
- the antibiotic is a sulfonamide.
- sulfonamides include and are not limited to afenide, prontosil, sulfacetamide, sulfamethiazole, sulfanamide, sulfasalazine, sulfisoxazole, trimethoprim, cotrimoxazole or the like.
- the antibiotic is a tetracycline antibiotic.
- tetracyclines include and are not limited to demeclocycline, doxycycline, minocycline, oxytetracycline, tetraycline or the like.
- the antibiotic is an oxazolidinone antibiotic.
- oxazolidinone antibiotics include and are not limited to linezolid or the like.
- the antibiotic is arsogebanubem chloramphenicol, clindamycin, lincomycin, ethambutol, fosfomycin, fusidic acid, furazolidone, isoniazid, linezolid, metronidazole, mupirocin, nitrofurantoin, platensimycin, pyrazinamide, quinupristin, dalfopristin, rifampicin, thamphenicol, tinidazole or the like.
- an antibiotic compatible with the compositions described herein is a broad spectrum antibiotic.
- an antibiotic compatible with the compositions described herein is effective in treating infections that are resistant to other classes of antibiotics.
- vancomycin is effective in treating infections caused by methicillin resistant staphyloccocus aureus bacteria.
- a antibacterial agent is a peptide or a lantibiotic including, by way of non-limiting example, Maximin H5, Dermcidin, Cecropins, andropin, moricin, ceratotoxin, melittin, Magainin, dermaseptin, bombinin, brevinin-l,esculentins and buforin II, CAP 18, LL37 , abaecin, apidaecins, prophenin, indolicidin, brevinins, protegrin, tachyplesins, defensins, drosomycin, alamethicin, pexiganan or MSI-78, and other MSI peptides like MSI-843 and MSI-594, polyphemusin, Class I II and III bacterocins like: colicin, pyocin, klebicin, subtilin, epidermin, herbicolacin, brevicin, halocin ,
- the antibiotic is a polypeptide or peptide.
- polypeptide antibiotics include and are not limited to bacitracin, colistin, polymyxin B or the like.
- peptide antibacterial agents include and are not limited to OP- 145 (Octoplus).
- an antibiotic used in formulations described herein is ciprofloxacin (Cipro®).
- an antibiotic used in formulations described herein is amoxicillin.
- an antibiotic used in formulations described herein is, amoxicillin + clavulanic acid (Augmentin®).
- an antibiotic used in formulations described herein is moxifloxacin.
- Localized administration of sinonasal compositions described herein reduces the risk of development of resistance to antibiotics compared to the risk for development of antibiotic resistance when an antibiotic is administered systemically.
- the compositions described herein are effective for recurring intrasinusoidal diseases or conditions including, for example, recurring sinusitis without the need for changing treatment regimens (e.g., in response to development of antibiotic resistance).
- Antimicrobial agents also include antibacterial, antiviral, antifungal, antiprotozoal and/or anti-parasitic agents described in U.S. Appl. Nos. 12/427,663, 12/466,310, 12/472,034, 12/486,697, 12/493,61 1, 12/494,156, 12/500,486, 12/504,553, 12/506,091, 12/506, 127, 12/506,573, 12/506,616, and 12/506,664, the disclosure of antimicrobial agents described therein is incorporated herein by reference. Antimicrobial agents that are not disclosed herein but which are useful for the amelioration or eradication of sinonasal disorders are expressly included and intended within the scope of the embodiments presented.
- the active agent in a comosition described herein is an antiviral agent.
- the antiviral agents include but are not limited to acyclovir, famciclovir and valacyclovir.
- antiviral agents include abacavir, aciclovir, adfovir, amantadine, amprenavir, arbidol, atazanavir, artipla, brivudine, cidofovir, combivir, edoxudine, efavirenz, emtricitabine, enfuvirtide, entecavir, fomvirsen, fosamprenavir, foscarnet, fosfonet, ganciclovir, gardasil, ibacitabine, imunovir, idoxuridine, imiquimod, indinavir, inosine, integrase inhibitors, interferons, including interferon type III, interferon type II, interferon type I, lamivudine, lopinavir, loviride, MK-0518, maraviroc, moroxydine, nelfinavir, nevirapine, nexavir, nucleo
- the active agent in a comosition described herein is an antifungal agent.
- the antifungal agents include but are not limited to amrolfine, utenafine, naftifine, terbinafine, flucytosine, fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, voriconazole, clotrimazole, econazole, miconazole, oxiconazole, sulconazole, terconazole, tioconazole, nikkomycin Z, caspofungin, micafungin, anidulafungin, amphotericin B, liposomal nystastin, pimaricin, griseofulvin, ciclopirox olamine, haloprogin, tolnaftate, undecylenate, clioquinol,
- Antiparasitic agents include amitraz, amoscanate, avermectin, carbadox, diethylcarbamizine, dimetridazole, diminazene, ivermectin, macrofilaricide, malathion, mitaban, oxamniquine, permethrin, praziquantel, prantel pamoate, selamectin, sodium stibogluconate, thiabendazole, and combinations thereof.
- Corticosteroids including any agents that act at glucorticoid receptors
- other antiinflammatory steroids are compatible with the formulations disclosed herein.
- One advantage of the use of a formulation described herein is the greatly reduced systemic exposure to anti- inflammatory glucocorticoid steroids.
- the active pharmaceutical ingredient of a formulation described herein is prednisolone. In another embodiment the active pharmaceutical ingredient of a formulation described herein is dexamethasone. In an additional embodiment
- the active pharmaceutical ingredient of a formulation described herein is beclomethasone.
- the active pharmaceutical ingredient of a formulation described herein is triamcinolone.
- the active pharmaceutical ingredient of a formulation described herein is selected from 21- acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone,
- an anti-inflammatory agent is a non-steroidal antiinflammatory agent (NSAID).
- an anti-inflammatory agent is a topical steroid or salt thereof, including and not limited to mometasone, mometasone furoate, fluticasone, fluticasone propionate, or the like.
- Anti-inflammatory agents that are not disclosed herein but which are useful for the amelioration or eradication of intrasinusoidal and/or nasopharyngeal disorders are expressly included and intended within the scope of the embodiments presented.
- compositions disclosed herein are agents which reduce or ameliorate symptoms or effects as a result of an autoimmune disease and/or inflammatory disorder. Accordingly, some embodiments of the methods and compositions described herein incorporate the use of agents which block the effects of TNF-cc, including anti-TNF agents for treatment of sinonasal conditions associated with autoimmune disease and/or inflammation.
- anti-TNF agents include protein-based therapeutics, such as etanercept (ENBREL ® ), infliximab (REMICADE ® ), adalimumab (HUMIRA ® ) and golimumab (CNTO 148), and small molecule therapeutics, such as TACE inhibitors, IKK inhibitors or calcineurin inhibitors or combinations thereof.
- Calcineurin inhibitors are a group of structurally diverse small molecule immunomodulators which function through the inhibition of calcineurin function. Examples of calcineurin modulators include tacrolimus, pimecrolimus, cyclosporine or the like.
- IKK inhibitors are yet another structurally diverse group of small molecule immunomodulators, examples of which include and are not limited to PC-839, PS-1145, BMS-345541, SC-514 or the like.
- immunomodulator agents suitable for use in the methods and compositions described herein include and are not limited to:
- TACE inhibitors include and are not limited to Nitroarginine analog A, GW3333, TMI-1, BMS-561392, DPC-3333, TMI-2, BMS-566394, TMI-005, apratastat, GW4459, W-3646, IK-682, GI-5402, GI-245402, BB-2983, DPC-A38088, DPH-067517, R-618, CH-138 or the like.
- Interleukin inhibitors include and are not limited to Nitroarginine analog A, GW3333, TMI-1, BMS-561392, DPC-3333, TMI-2, BMS-566394, TMI-005, apratastat, GW4459, W-3646, IK-682, GI-5402, GI-245402, BB-2983, DPC-A38088, DPH-067517, R-618, CH-138 or the like.
- Interleukin inhibitors include and are not limited to WS-4 (an antibody against IL-8), SB 265610 (N-(2-Bromophenyl)-N'-(7-cyano-lH-benzotriazol-4-yl)urea); SB 225002 ( -(2-Bromophenyl)-N'-(2-hydroxy-4-nitrophenyl)urea); SB203580 (4-(4- Fluorophenyl)-2-(4-methylsulfinyl phenyl)-5-(4-pyridyl) lH-imidazole); SB272844 (GlaxoSmithKline); SB517785 (Glaxo SmithKline); SB656933 (GlaxoSmithKline);
- Sch527123 (2-hydroxy-N,N-dimethyl-3- ⁇ 2-[[(R)-l-(5-methyl-furan-2-yl)-propyl]amino]- 3,4-dioxo-cyclobut-l-enylamino ⁇ -benzamide); PD98059(2-(2-amino-3-methoxyphenyl)- 4H- 1 -Benzopyran-4-one); reparixin; N-[4-chloro-2-hydroxy-3-(piperazine-l- sulfonyl)phenyl]-N'-(2-chloro-3-fluorophenyl)urea p-toluenesulfonate, basiliximab;
- cyclosporin A SDZ RAD (40-O-(2-hydroxyethyl)-rapamycin); FR235222 (Astellas Pharma); daclizumab; anakinra; AF12198 (Ac-Phe-Glu-Trp-Thr-Pro-Gly-Trp-Tyr-Gln-L- azetidine-2-carbonyl-Tyr-Ala-Leu-Pro-Leu-NH2) or the like.
- Examples of platelet activating factor antagonists include and are not limited to kadsurenone, phomactin G, ginsenosides, apafant (4-(2- chlorophenyl)-9-methyl-2[3(4- morpholinyl)-3-propanol-l- yl[6H- thieno[3.2-f[[1.2.4]triazolo]4,3-l]]1.4]diazepine), A- 85783, BN-52063, BN-52021, BN-50730 (tetrahedra-4,7,8,10 methyl-1 (chloro-1 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo- 1,2,4 [4,3-a] diazepine-1,4), BN 50739, SM-12502, RP-55778, Ro 24-4736, SR27
- Examples of toll like receptor inhibitors include and are not limited to E5531 ((6-0- ⁇ 2-deoxy-6-0-methyl-4-0-phosphono-3-0-[(R)-3-Z-dodec-5-endoyloxydecl]-2-[3-oxo- tetradecanoylamino]- -0-phosphono-a-D-glucopyranose tetrasodium salt); E5564 (a-D- Glucopyranose,3-0-decyl-2-deoxy-6-0-[2-deoxy-3-0-[(3R)-3-methoxydecyl]-6-0-methyl- 2- [ [( 11 Z)- 1 -oxo- 11 -octadecenyl] amino] -4-0-phosphono- -D-glucopyranosyl]-2- [( 1,3- dioxotetradecyl)amino]-l-(dihydrogen phosphate), tetra
- progesterone receptor modulators include and are not limited to RU-486 ((1 lb,17 b)-l l-[4-(Dimethylamino)phenyl]-17-hydroxy-17-(l-propyn yl)-estra-4,9-dien-3- one); CDB-2914 (17a-acetoxy-l l -[4-N,N-dimethylaminophenyl]-19-norpregna-4,9-diene- 3,20-dione); CDB-4124 (17a-acetoxy-21-methoxy-l l -[4-N,N-dimethylaminophenyl]-19- norpregna-4,9- diene-3,20-dione); CDB-4453 (17a-acetoxy-21-methoxy-l l -[4-N- methylaminophenyl]-19-norpregna-4,9-diene-3,20-dione); RTI 3021-022
- prostaglandins and/or analogs thereof include and are not limited to naturally occurring prostaglandins, Prostaglandin analogues, such as latanoprost, travoprost, unoprostone, minprostin F2 alpha and bimtoprost, SQ29548, JB004/A or the like.
- Examples of adenosine receptor modulators include and are not limited to ATL313 (4-(3-(6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin- 2-yl)prop-2-ynyl)piperidine-l-carboxylic acid methyl ester); GW328267X ((2R,3R,4S,5R)- 2- ⁇ 6-amino-2-[(l-benzyl-2-hydroxyethyl)amino]-9H-purin-9-yl ⁇ -5-(2-ethyl-2H-tetrazol-5- yl)tetrahydrofuran-3,4-diol); CGS 21680 hydrochloride (4-[2-[[6-Amino-9-( -ethyl-b-D- ribofuranuronamidosyl)-9H -purin-2
- Contemplated for use with the formulations disclosed herein are agents which reduce or ameliorate symptoms or effects as a result of a cell proliferation disorder.
- some embodiments of the methods and compositions described herein incorporate the use of cytotoxic agents for treatment of sinonasal and/or nasopharyngeal conditions including and not limited to cancers.
- cytotoxic agents include and are not limited to antibodies
- antimetabolites and other anticancer agents such as methotrexate (RHEUMATREX®, Amethopterin) cyclophosphamide (CYTOXAN®), thalidomide (THALIDOMID®), acridine carboxamide, actimid®, actinomycin, 17-N-allylamino-17- demethoxygeldanamycin, aminopterin, amsacrine, anthracycline, antineoplastic, antineoplaston, 5-azacytidine, azathioprine, BL22, bendamustine, biricodar, bleomycin, bortezomib, bryostatin, busulfan, calyculin, camptothecin, capecitabine, carboplatin, chlorambucil, cisplatin, cladribine, clofarabine, cytarabine, dacarbazine, dasatinib, daunorubicin, decitabine, dich
- cytotoxic agents are described in, for example, U.S. Appl. No. 12/493,61 1, which agents are incorporated herein by reference.
- Contemplated for use with the formulations disclosed herein are agents which modulate estrogen receptors in sinonasal epithelia. Accordingly, some embodiments of the methods and compositions described herein incorporate the use of estrogen receptor modulators for treatment of sinonasal conditions including and not limited to polyps and/or cancers in the sinonasal structures.
- estrogen receptor modulators include and are not limited to, PPT (4,4',4"-(4-Propyl-[lH]-pyrazole-l,3,5-triyl)trisphenol); SKF-82958 (6-chloro-7,8-dihydroxy-3-allyl-l-phenyl-2,3,4,5-tetrahydro-lH-3-benzazepine); estrogen; estradiol; estradiol derivatives, including but not limited to 17- ⁇ estradiol, estrone, estriol, synthetic estrogen compositions or combinations thereof.
- the ⁇ agonist is ⁇ -131, phytoestrogen, MK 101 (bioNovo); VG-1010 (bioNovo); DPN
- Contemplated for use with the formulations disclosed herein are agents which modulate epithelial cell growth. Accordingly, some embodiments of the methods and compositions described herein incorporate the use of growth factors and/or modulators of growth factors for treatment of sinonasal conditions associated with aberrant growth in sinonasal cavities.
- growth factors contemplated for incorporation in compositions described herein include, for example, fibroblast growth factor (FGF), insulinlike growth factor (IGF), epidermal growth factor (EGF), a platlet-derived growth factor (PGF), agonists of epidermal growth factor (EGF) receptor, hepatocyte growth factor (HGF), Transforming growth factor alpha (TGF-a), Transforming growth factor beta (TGF- ⁇ ), modulators of Vascular endothelial growth factor (VEGF) or the like.
- FGF fibroblast growth factor
- IGF insulinlike growth factor
- EGF epidermal growth factor
- PEF platlet-derived growth factor
- HGF hepatocyte growth factor
- TGF-a Transforming growth factor alpha
- TGF- ⁇ Transforming growth factor beta
- VEGF Vascular endothelial growth factor
- apoptosis modulators for treatment of sinonasal conditions associated with aberrant apoptosis.
- Inhibitors of apoptosis include inhibitors of the MAPK/J K signaling cascade AKT inhibitors, IKK inhibitors, JAK inhibitors, PI3 kinase inhibitors, NF- ⁇ inhibitors, p38 inhibitors, ERK inhibitors, Src inhibitors or the like that are involved in apoptotic pathways.
- Other modulators of apoptotic pathways included modulators of caspases or sirtuin.
- the anti-apoptotic agent is an agent which inhibits (partially or fully) the activity of the MAPK/JNK signaling cascade.
- the anti- apoptotic agent is minocycline; SB-203580 (4-(4-Fluorophenyl)-2-(4-methylsulfinyl phenyl)-5-(4-pyridyl) lH-imidazole); PD 169316 (4-(4-Fluorophenyl)-2-(4-nitrophenyl)-5- (4-pyridyl)-lH-imidazole); SB 202190 (4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4- pyridyl)lH-imidazole); RWJ 67657 (4-[4-(4-fluorophenyl)-l-(3-phenylpropyl)-5-(4-
- the agent which antagonizes the MAPK/JNK signaling cascade is D-JNKI-1 ((D)-hJIPi 75 _ 15 7-DPro-DPro-(D)-HIV-TAT 5 7-48), AM-11 1 (Auris), SP600125 (anthra[l,9-cd]pyrazol- 6(2H)-one), JNK Inhibitor I ((L)-HIV-TAT 48 -57-PP-JBD 2 o), JNK Inhibitor III ((L)-tflV- TAT 47 -57-gaba-c-Jun5 3 3-57), AS601245 (l,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino] -4 pyrimidinyl) acetonitrile), JNK Inhibitor VI (H 2 N-RPKRPTTLNLF-NH 2 ), JNK Inhibitor VIII (
- JAK Janus Kinase
- the anti-apoptotic agent is VX-680, TG101348, TG101209, I CB018424, XL019, CEP-701, AT9283, or combinations thereof.
- the anti-apoptotic agent is an agent that inhibits (partially or fully) the activity of Aktl .
- the anti-apoptotic agent is a growth factor.
- the growth factor is EGF.
- the anti-apoptotic agent is an agent that inhibits (partially or fully) the activity of PI3 kinases.
- the anti-apoptotic agent is 740 Y-P; SC 3036 (KKHTDDGYMPMSPGVA); PI 3-kinase Activator (Santa Cruz Biotechnology, Inc.), wortmannin, wortmannin analogs (e.g., PX-866); or combinations thereof.
- agents that modulate an NF-kB transcription factor incorporate the use of agents that modulate an NF-kB transcription factor.
- the agent that modulates an NF-kB transcription factor is an antagonist, partial agonist, inverse agonist, neutral or competitive antagonist, allosteric antagonist, and/or orthosteric antagonist of NF-kB.
- the NF- kB transcription factor agonist, partial agonist, and/or positive allosteric modulator is Pam 3 Cys ((S)-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys4- OH, trihydrochloride); Actl (NF-kB activator 1); Acetyl- 1 1-keto-b-Boswellic Acid;
- Andrographolide Caffeic Acid Phenethyl Ester (CAPE); Gliotoxin; Isohelenin; NEMO- Binding Domain Binding Peptide (DRQIKIWFQNRRMKWKKTALDWSWLQTE); NF- kB Activation Inhibitor (6-Amino-4-(4-phenoxyphenylethylamino)quinazoline); NF-kB Activation Inhibitor II (4-Methyl-Nl-(3-phenylpropyl)benzene-l,2-diamine); NF-kB Activation Inhibitor III (3-Chloro-4-nitro-N-(5-nitro-2-thiazolyl)-benzamide); NF-kB Activation Inhibitor IV ((E)-2-Fluoro-4'-methoxystilbene); NF-kB Activation Inhibitor V (5-Hydroxy-(2,6-diisoprop
- agents that modulate p38 are a p38 antagonist, partial agonist, inverse agonists, neutral or competitive antagonists, allosteric antagonists, and/or orthosteric antagonists.
- the p38 antagonist, partial agonist, inverse agonists, neutral or competitive antagonist, allosteric antagonist, and/or orthosteric antagonist is ARRY-797 (Array BioPharma); SB-220025 (5-(2-Amino-4-pyrimidinyl)-4-(4- fluorophenyl)- l-(4-piperidinlyl)imidazole); SB-239063 (trans-4-[4-(4-Fluorophenyl)-5-(2- methoxy-4-pyrimidinyl) -lH-imidazol-l-yl]cyclohexanol); SB-202190 (4-(4- Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)lH-imidazole); JX-401 (-[2-Methoxy-4- (methylthio)benzoyl]-4-(phenylmethyl)piperidine); PD-169316 (4-(4-Flu
- Src modulators Contemplated for use in the methods and compositions described herein are Src modulators.
- the Src antagonist, partial agonist, inverse agonist, neutral or competitive antagonist, allosteric antagonist, and/or orthosteric antagonist is 1- Naphthyl PPl (l-(l,l-Dimethylethyl)-3-(l-naphthalenyl)-lH-pyrazolo[3, 4-d]pyrimidin-4- amine); Lavendustin A (5-[[(2,5-Dihydroxyphenyl)methyl][(2-hydroxyphenyl)methy l]amino]-2-hydroxybenzoic acid); MNS (3,4-Methylenedioxy-b-nitrostyrene); PPl (1-(1,1- Dimethylethyl)-l-(4-methylphenyl)-lH-pyrazolo[3, 4-d]pyrimidin-4-amine); PP2 (3-(4- chlorophenyl)
- Bosutinib (4-((2,4-dichloro-5-methoxyphenyl)amino)-6- methoxy-7-(3-(4-methyl-l-piperazinyl)propoxy)-3-quinolinecarbonitrile); or combinations thereof.
- an antagonist, partial agonist, inverse agonist, neutral or competitive antagonist, allosteric antagonist, and/or orthosteric antagonist of a caspase target is suitable for use in methods and compositions described herein.
- the caspase inhibitor is z-VAD- FMK (Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone); z-LEHD-FMK (benzyloxycarbonyl-Leu-Glu(OMe)-His-Asp(OMe)-fluoromethylketone); B-D-FMK (boc- aspartyl(Ome)-fluoromethylketone); Ac-LEHD-CHO (N-acetyl-Leu-Glu-His-Asp-CHO); Ac-IETD-CHO ( -acetyl-Ile-Glu-Thr-Asp-CHO); z-IETD-FMK (benzyloxycarbonyl-Ile- Glu(OMe)-Thr-Asp(OMe)-fluoromethy lketone); FAM-LEHD-FMK (benzyloxycarbonyl Leu-Glu-His-Asp-fluoromethyl ketone); FAM-LEHD
- Some embodiments incorporate the use of one or more antagonists, partial agonists, inverse agonists, neutral or competitive antagonists, allosteric antagonists, and/or orthosteric antagonists of sirtuins.
- the agonist, partial agonist, and/or positive allosteric modulator of sirtuin activity is a stilbene, flavone, isoflavone, flavanone, catechin, free radical protective compound, isonicotinamide, dipyridamole, ZM 336372 (3- (dimethylamino)-N-[3-[(4-hydroxybenzoyl)-amino]-4-met hylphenyljbenzamide), camptothecin, coumestrol, nordihydroguaiaretic acid, esculetin, SRT-1720 (Sirtris), SRT- 1460 (Sirtris), SRT-2183 (Sirtris), resveratrol, piceatannol, rhap
- Contemplated for use with the formulations disclosed herein are agents which reduce or ameliorate symptoms or effects as a result of wheal and flare in sinonasal passages. Accordingly, some embodiments of the methods and compositions described herein incorporate the use of antihistamines for treatment of sinonasal conditions.
- antihistamines suitable for methods and compositions described herein include, but are not limited to, meclizine, diphenhydramine, loratadine, levocetirizine, fexofenadine, quetiapine, mepyramine, piperoxan, antazoline, carbinoxamine, doxylamine, clemastine, dimenhydrinate, pheniramine, chlorphenamine, chlorpheniramine,
- Contemplated for use with the formulations disclosed herein are agents which reduce or ameliorate symptoms or effects as a result of aberrant ion channel activity in epithelial cells lining sinusoidal or nasal cavities.
- aberrant NMDA receptor activity is associated with influx of Ca 2+ and/or Na + ions in epithelial cells.
- NMDA receptor antagonists include and are not limited to aminoadamantane, dextromethorphan, dextrorphan, ibogaine, ketamine (including R or S ketamine), nitrous oxide, phencyclidine, riluzole, tiletamine, memantine, neramexane, dizocilpine, aptiganel, remacimide, 7-chlorokynurenate, DCKA (5,7-dichlorokynurenic acid), kynurenic acid, 1 -aminocyclopropanecarboxylic acid (ACPC), AP7 (2-amino-7- phosphonoheptanoic acid), APV (R-2-amino-5-phospho
- the agent that modulates ion channel activity in sinonasal epithelia is a modulator of ENaC channels.
- the epithelial sodium channel (ENaC, sodium channel non-neuronal 1 (SCNN1) or amiloride sensitive sodium channel (ASSC)) is a membrane-bound ion-channel that is permeable for Li + -ions, protons and Na + -ions.
- ENaC is located in the apical membrane of polarized epithelial cells and is involved in transepithelial Na + -ion transport. Na + /K+-ATPase is also involved in Na + transport and ion homeostasis.
- modulators of the activity of ENaC include, by way of example, the mineralcorticoid aldosterone, triamterene, and amiloride.
- the agent that modulates ion channel activity in sinonasal epithelia is a calcium channel agonist or antagonist.
- the calcium channel antagonist is cinnarizine, flunarizine, or nimodipine.
- Other calcium channel blockers include and are not limited to verapamil, diltiazem, omega-conotoxin, GVIA, amlodipine, felodipine, lacidipine, mibefradil, NPPB (5-Nitro-2-(3- phenylpropylamino)benzoic Acid), flunarizine, and/or combinations thereof
- the agent that modulates ion channel activity in sinonasal epithelia is a potassium channel agonist or antagonist.
- the the agonist of a potassium channel is nicorandil; minoxidil, levcromakalim; lemakalim; cromakalim; L- 735,334 (14-hydroxy CAF-603 oleate); retigabine; flupirtine; BMS-204352 (3S)-(+)-(5- Chloro-2-methoxyphenyl)- 1 ,3 -dihydro-3 -fluoro-6-(trifluoromethyl)-2H-indole-2-one); DMP-543 (10, 10-bis((2-fluoro-4-pyridinyl)methyl)-9(10H)-anthracenone); or combinations thereof.
- the agent that modulates a potassium channel is an antagonist of a potassium channel (e.g. a potassium channel blocker).
- the antagonist of a potassium channel is linopirdine; XE991 (10,10-bis(4-pyridinylmethyl)- 9(10H)-anthracenone); 4-AP (4-aminopyridine); 3,4-DAP (3,4-Diaminopyridine); E-4031 (4'-[[l-[2-(6-methyl-2-pyridyl)ethyl]-4-piperidinyl]carbonyl]-methanesulfonanilide); DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid); Way 123,398 (N-methyl-N-(2-(methyl(l- methyl-lH-benzimidazol-2-yl)amino)ethyl)-4-((methylsulfonyl)
- benzenesulfonamide HC1 CGS-12066A (7-Trifluoromethyl-4-(4-methyl-l- piperazinyl)pyrrolo-[l,2-a]quinoxaline); dofetilide; sotalol; apamin; amiodarone; azimilide; bretylium; clofilium; tedisamil; ibutilide; sematilide; nifekalant; tamulustoxin and combinations thereof.
- the agent that modulates ion channel activity in sinonasal epithelia is a sosium channel agonist or antagonist.
- a Na + channel blocker is vinpocetine ((3a, 16a)-Eburnamenine-14-carboxylic acid ethyl ester); sipatrigine (2-(4-Methylpiperazin-l-yl)-5-(2,3,5-trichlorophenyl)-pyrimidin-4-amine); amiloride (3,5- diamino-N-(aminoiminomethyl)-6-chloropyrazinecarbox amide hydrochloride);
- the agent that modulates ion channel activity in sinonasal epithelia is an AMPA receptor antagonist.
- the agent which antagonizes the AMPA receptors is CNQX (6-cyano-7-nitroquinoxaline-2,3-dione); NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione); DNQX (6,7- dinitroquinoxaline-2,3-dione); kynurenic acid; 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo- [fjquinoxaline; or combinations thereof.
- an agent that modulates ion channel activity in sinonasal epithelia indirectly controls the opening of ion channels by the activation of biochemical cascades.
- the agent is a modulator of mGlu receptors.
- agents that are group II mGlu receptor agonists include and are not limited to LY389795 ((-)-2-thia-4-aminobicyclo-hexane-4,6-dicarboxylate); LY379268 ((-)- 2-oxa-4-aminobicyclo-hexane-4,6-dicarboxylate); LY354740 ((+)-2-aminobicyclo-hexane- 2,6dicarboxylate); DCG-IV ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine); 2R,4R- APDC (2R,4R-4-aminopyrrolidine-2,4-dicarboxylate), (S)-3C4HPG ((S)-3-carboxy-4- hydroxyphenylglycine); (S)-4C3HPG ((S)-4-carboxy-3-hydroxyphenylglycine); L-CC
- agents that are group III mGlu receptor agonists include and are not limited to ACPT-I ((1 S,3R,4S)-1- aminocyclopentane-l,3,4-tricarboxylic acid); L-AP4 (L-(+)-2-Amino-4-phosphonobutyric acid); (S)-3,4-DCPG ((S)-3,4-dicarboxyphenylglycine); (RS)-3,4-DCPG ((RS)-3,4- dicarboxyphenylglycine); (RS)-4-phosphonophenylglycine ((RS)PPG); AMN082 (, ⁇ '- bis(diphenylmethyl)-l,2-ethanediamine dihydrochloride); DCG-IV ((2S,2'R,3'R)-2-(2',3'- dicarboxycyclopropyl)glycine); or the like.
- ACPT-I ((1 S,3R,4S)-1- aminocyclopent
- mGlu receptor modulators include and are not limited to is 3,5-Dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(l,2,2- trimethyl-propyl) ester (3,5-dimethyl PPP); 3,3'-difluorobenzaldazine (DFB), 3,3'- dimlethoxybenzaldazine (DMeOB), 3,3'-dichlorobenzaldazine (DCB) and other allosteric modulators of mGluR 5 disclosed in Mol. Pharmacol.
- DFB 3,3'-difluorobenzaldazine
- DMeOB 3,3'- dimlethoxybenzaldazine
- DCB 3,3'-dichlorobenzaldazine
- the agent that modulates ion channel activity in sinonasal epithelia is an TRPV1 agonist or antagonist.
- an agonist of one or more of the TRPV receptors is capsaicin, resiniferatoxin, or combinations thereof.
- ion channel modulators include purinergic receptor modulators, GABA receptor modulators or the like. Ion channel modulators described in U.S. Appl. Nos. 12/506,664, 12/427,663, and 12/494, 156 are incorporated herein by reference and are contemplated as being within the scope of embodiments presented herein.
- the formulations provided herein allow for sustained release of anti-angiogenic in the intrasinusoidal and/or nasal and/or
- the anti-angiogenesis agent is a modulator of the VEGF1 and/or VEGF2 receptor(s).
- anti-angiogenic agents include and are not limited to bevacizumab (Avastin®), thalidomide, linomide,TNP-470, matrix metalloprotease inhibitors, VEGFR antagonists, and the like.
- the formulations disclosed herein allow for sustained release of immunosuppressants in an affected area for long term treatment of condition such as, for example, Wegerner's granulomatosis. Further, the intrasinusoidal and/or nasal and/or nasopharyngeal formulations described herein are administered with reduced dosing frequency thereby improving patient compliance and comfort where long term therapy is indicated. Examples of immunosuppressants include and are not limited to Cyclosporine, 6-MP, and Methotrexate.
- an immunosuppresant is an agent that acts at glucocorticoid receptors (e.g., any glucocorticoid described herein, including and not limited to Hydrocortisone, Cortisone, Prednisone, Prednisolone,
- Methylprednisolone Dexamethasone, Betamethasone, Triamcinolone, Beclometasone, Fludrocortisone acetate, Aldosterone or the like).
- RNA interference are utilized.
- the agent that inhibits or down-regulates the target is an siRNA molecule.
- the siRNA molecule inhibits the transcription of a target by RNA interference (RNAi).
- RNAi RNA interference
- dsRNA double stranded RNA
- a 20-25 bp siRNA molecule with sequences complementary to a target is generated.
- the 20-25 bp siRNA molecule has 2-5 bp overhangs on the 3' end of each strand, and a 5' phosphate terminus and a 3 ' hydroxyl terminus. In some embodiments, the 20-25 bp siRNA molecule has blunt ends.
- Molecular Cloning A Laboratory Manual, second edition (Sambrook et al, 1989) and Molecular Cloning: A Laboratory Manual, third edition (Sambrook and Russel, 2001), jointly referred to herein as
- the dsRNA or siRNA molecule is incorporated into a sustained-release formulation described herein and is injected into or in the vicinity of the sinonasal cavity or structure.
- the dsRNA or siRNA molecule after administration of the dsRNA or siRNA molecule, cells at the site of administration (e.g. the cells of sinonasal passages) are transformed with the dsRNA or siRNA molecule.
- the dsRNA molecule is cleaved into multiple fragments of about 20-25 bp to yield siRNA molecules.
- the fragments have about 2bp overhangs on the 3' end of each strand.
- an siRNA molecule is divided into two strands (the guide strand and the anti-guide strand) by an RNA-induced Silencing Complex (RISC).
- the guide strand is incorporated into the catalytic component of the RISC (i.e. argonaute).
- the guide strand binds to a complementary target mRNA sequence.
- the RISC cleaves the target mRNA.
- the expression of the target gene is down-regulated.
- a sequence complementary to a target is ligated into a vector.
- the sequence is placed between two promoters.
- the promoters are orientated in opposite directions.
- the vector is contacted with a cell.
- a cell is transformed with the vector.
- sense and anti-sense strands of the sequence are generated.
- the sense and anti-sense strands hybridize to form a dsR A molecule which is cleaved into siRNA molecules.
- the strands hybridize to form an siRNA molecule.
- the vector is a plasmid (e.g pSUPER; pSUPER.neo; pSUPER.neo+gfp).
- the vector is incorporated into a sustained release
- microsphere or microparticle hydrogel, liposome, or thermoreversible gel.
- agents that are suitable for use in intrasinusoidal and/or nasal and/or nasopharyngeal formulations described herein include agents that modulate activity of epithelial cells lining the sinonasal cavities and/or passages.
- agents that modulate the activity of epithelial cells include and are not limited to modulators of the PTEN pathway; modulators of PPAR; modulators of EGFR; growth factors including and not limited to TGF-beta, and fibroblast growth factor; and/or modulators of epithelial cell adhesion.
- agents suitable for use in sinonasal formulations described herein include agents that modulate synthesis and/or activity of keratin (e.g., actinomycin D, vitamin A, or the like).
- agents that are suitable for use in sinonasal formulations described herein include agents that modulate eosinophils and/or inflammatory cytokines. Examples of agents that modulate the activity of eosinophils and/or
- inflammatory cytokines include and are not limited to leukotriene blockers (e.g., monteleukast, Singulair®), prostaglandin D 2 receptor (PGD2) modulators, lipophosphatidic acid receptor (LP A) modulators, 5-lipoxygenase activating protein (FLAP) modulators, CRTH2 (DP2) modulators, or the like.
- leukotriene blockers e.g., monteleukast, Singulair®
- PGD2 prostaglandin D 2 receptor
- LP A lipophosphatidic acid receptor
- FLAP 5-lipoxygenase activating protein
- DP2 CRTH2
- agents suitable for use in sinonasal formulations described herein include agents that modulate cadherins (e.g., Trichostatin A, ADH1 (Molecular and Cellular Neuroscience, 28, 2005, 253-263),
- compositions comprising a combination of one or more than one active agent, including any active agent described herein.
- compositions that comprise an antimicrobial agent in combination with an antiinflammatory agent.
- a formulation described herein comprises an antibiotic in combination with an anti-inflammatory agent (e.g., any anti-inflammatory agent described herein).
- a formulation described herein comprises an antibiotic (e.g., any antibiotic described herein) in combination with a corticosteroid.
- a composition comprising an antibiotic and a corticosteroid has different release profiles for each of the active agents. In other embodiments, a composition comprising an antibiotic agent and a corticosteroid agent has substantially similar release profiles for each of the active agents.
- a formulation described herein comprises an antibiotic in combination with dexamethasone. In certain embodiments, a formulation described herein comprises an antibiotic in combination with methylprednisolone or prednisolone. In certain embodiments, a formulation described herein comprises ciprofloxacin in combination with dexamethasone. In certain embodiments, a formulation described herein comprises moxifloxacin in combination with dexamethasone. In certain embodiments, a formulation described herein comprises ofloxacin in combination with dexamethasone. In certain embodiments, a formulation described herein comprises ciprofloxacin in combination with methylprednisolone or prednisolone or triamcinolone.
- a composition comprising an antibiotic and a corticosteroid contains one or both active agents as multiparticulates (e.g., as micronized active agents).
- active agents e.g., as micronized active agents.
- a composition comprising water soluble dexamethasone and multiparticulates of a form of ciprofloxacin with poor water solubility provides extended release of dexamethasone for at least 3 days and extended release of ciprofloxacin for at least 10 days.
- a composition comprising multiparticulates (e.g., micronized particles) of a form of dexamethasone with poor water solubility, and a water soluble form of ciprofloxacin provides extended release of ciprofloxacin for at least 3 days and extended release of dexamethasone for at least 10 days.
- a composition comprising
- multiparticulates e.g., micron-sized particles, nanoparticles, non-sized particles
- mulitparticulates e.g., micron-sized particles, nanoparticles, non-sized particles
- ciprofloxacin with poor water solubility
- active agents suitable for combination therapy include and are not limited to agents described herein, and agents described in U.S. Appl. Nos. 12/427,663, 12/466,310, 12/472,034, 12/486,697, 12/493,611, 12/494, 156, 12/500,486, 12/504,553, 12/506,091, 12/506, 127, 12/506,573, 12/506,616, and 12/506,664, agents described therein are incorporated herein by reference.
- any formulation described herein is used in combination with a mechanical or imaging device to monitor or survey the sinonasal disorder (e.g., deformed turbinate, nasal polyps).
- a mechanical or imaging device to monitor or survey the sinonasal disorder (e.g., deformed turbinate, nasal polyps).
- MRI magnetic resonance imaging
- the MRI devices for example, 3 Tesla MRI devices
- disease progression e.g., progression of Meniere's disease
- formulations described herein comprise Gadolinium-based dyes, iodine-based dyes, barium-based dyes, or the like and are used in the treatment of any sinonasal disorder described herein and/or with any mechanical or imaging device or method described herein (e.g., a CAT scan).
- any mechanical or imaging device or method described herein e.g., a CAT scan.
- Such formulations allow for visualization of disease progression and/or formulation penetration in the sinonasal cavities and/or therapeutic effectiveness of the formulation.
- an imaging agent e.g., gadolinium hydrate injection
- 3D-real IR three-dimensional real inversion recovery
- 3D-FLAIR three-dimensional fluid-attenuated inversion recovery
- MRI magnetic resonance imaging
- the compositions described herein include a dye to help enhance the visualization of penetration of the formulation in the sinonasal cavities.
- dyes that are compatible with the compositions described herein include and are not limited to Evans blue, Methylene blue, Isosulfan blue, Trypan blue, indocyanine green or the like.
- intrasinusoidal and/or nasal and/or nasopharyngeal formulations described herein in combination with devices and/or techniques used during sinonasal surgery.
- surgical devices include the AdvaCoatTM Sinus Dressing and the AdvaCoatTM Rx for chronic rhinosinusitis (available from Carbylan BioSurgery, Inc) which comprise injectable devices that bind covalently to tissues at a target delivery site.
- a intrasinusoidal and/or nasal and/or nasopharyngeal formulation described herein in combination with the aforementioned devices are examples of such surgical devices.
- AdvaCoatTM Sinus Dressing and the AdvaCoatTM Rx for chronic rhinosinusitis (available from Carbylan BioSurgery, Inc) which comprise injectable devices that bind covalently to tissues at a target delivery site.
- a intrasinusoidal and/or nasal and/or nasopharyngeal formulation described herein in combination with the a
- an intrasinusoidal and/or nasal and/or nasopharyngeal formulation described herein is used in combination with endoscopic, catheter-based tools such as the Balloon SinuplastyTM devices available from Acclarent.
- an intrasinusoidal and/or nasal and/or nasopharyngeal formulation described herein is used in combination with a bioabsorbable drug eluting stent such as a stent available from Intersect ENT, Inc.
- sterilization means a process used to destroy or remove
- microorganisms and/or pyrogens that are present in a product or packaging.
- Available methods for the inactivation of microorganisms include, but are not limited to, the application of extreme heat, lethal chemicals, or gamma radiation.
- Heat sterilization methods include the use of a saturated steam autoclave at a temperature of at least 121 °C, or dry heat sterilization (e.g., heating a dry powder for about 3 - 1 1 hours at internal powder temperatures of 130-140 °C, or for 1-2 hours at internal temperatures of 150-180 °C).
- Filtration sterilization is a method used to remove microorganisms from solutions.
- a formulation is subjected to terminal sterilization.
- the formulation that is autoclaved comprises the active agent and all the excipients.
- all the excipients are subjected to heat sterilization and the active agent is sterilized separately; the active agent and the excipients are then mixed aseptically.
- the active agent is sterilized separataely (e.g., dry-heat sterilized, irradiated, steam-sterilized) and the other excipients are sterile- filtered; the sterile active agent and the sterile-filtered solution are then mixed aseptically.
- a sterile suspension of active agent in a solution comprising a thermosetting polymer is aseptically mixed with a second solution comprising a thermosetting polymer and optionally a second active agent.
- compositions e.g., intrasinusoidal formulations
- an appropriate thermosetting polymer in combination with a specific buffer and/or pH range for the formulation allows for high temperature terminal sterilization of formulations described herein with substantially low degradation of the therapeutic agent and/or the polymeric excipients.
- any appropriate buffer is used depending on the active agent used in the formulation.
- autoclaving at 250°F (121°C) results in a significant downward pH shift (i.e. more acidic) in the TRIS buffer whereas a relatively much less upward pH shift in the PBS buffer and therefore much increased hydrolysis and/or degradation of an active agent in TRIS than in PBS.
- Degradation of an active agent and/or polymeric components is reduced by the use of an appropriate combination of a buffer and concentration of thermoreversible polymer.
- any controlled release formulation described herein has less than about 100 colony forming units, less than about 60 colony forming units, less than about 50 colony forming units, less than about 40 colony forming units, or less than about 30 colony forming units of microbial agents per gram of formulation.
- the sterile formulations described herein are substantially free of microbes.
- An additional aspect of the sterilization process is the removal of by-products from the killing of microorganisms.
- the process of depyrogenation removes such pyrogens from the sample.
- endotoxin units One EU is equivalent to 100 picograms of E. coli LPS. Humans can develop a response to as little as 5 EU/kg of body weight.
- sinonasal compositions described herein contain lower endotoxin levels (e.g.
- the formulations described herein are substantially free of pyrogens.
- any formulation disclosed herein e.g., an intrasinusoidal formulation, a nasopharyngeal formulation
- nasopharyngeal formulation provided herein is formulated to provide an ionic balance that is compatible with sinonasal fluids and thereby minimizes irritation to the tissues.
- osmolarity/osmolality means the osmolarity/osmolality of a formulation as determined by measuring the osmolarity/osmolality of the active agent and all excipients except the thermoreversible polymer agent (e.g., polyoxyethylene-polyooxypropylene copolymers, or the like).
- the practical osmolarity of a formulation disclosed herein is measured by any suitable method, e.g., a freezing point depression method as described in Viegas et. al, Int. J. Pharm., 1998, 160, 157-162.
- the practical osmolarity of a formulation disclosed herein is measured by vapor pressure osmometry (e.g., vapor pressure depression method) that allows for determination of the osmolarity of a formulation at higher temperatures.
- vapor pressure depression method allows for determination of the osmolarity of a formulation comprising a a thermoreversible polymer at a higher temperature such as for example the gelation temperature of the thermoreversible polymer.
- the osmolarity at a target site of action is about the same as the practical osmolarity of a formulation described herein.
- the practical osmolality of a sinonasal formulation disclosed herein is from about 100 mOsm/kg to about 1000 mOsm/kg, from about 200 mOsm/kg to about 800 mOsm/kg, from about 250 mOsm/kg to about 500 mOsm/kg, or from about 250 mOsm/kg to about 320 mOsm/kg, or from about 250 mOsm/kg to about 350 mOsm/kg or from about 280 mOsm/kg to about 320 mOsm/kg.
- a formulation described herein has a practical osmolarity of about 100 mOsm/L to about 1000 mOsm/L, about 200 mOsm/L to about 800 mOsm/L, about 250 mOsm/L to about 500 mOsm/L, about 250 mOsm/L to about 350 mOsm/L, about 250 mOsm/L to about 320 mOsm/L, or about 280 mOsm/L to about 320 mOsm/L.
- the practical osmolality is estimated as an additive combination of buffer osmolality and the osmolality of the supernatant of the gelled poloxamer in water.
- the practical osmolality of a formulation described herein is measured in a cell-based assay.
- the osmolality experienced by red blood cells isolated from guinea pigs was determined as a function of the hemolysis index.
- RBCs were placed in poloxamer solutions of varying concentrations. 0.5 mL of 10% guinea pig red blood cells in saline was added into a 2.5 mL solution of poloxamer 407 in buffer. The resulting suspension was serially diluted and the hemolysis index of RBCs was recorded for each solution.
- the hemolysis index is defined as the ratio of absorbance of a sample at 540 nm to the absorbance of a 0.9% saline solution at 540 nm.
- a hemolysis index of 1 indicates that the "practical osmolality" experienced by the RBCs is suitable for sinonasal administration.
- the RBCs are intact in media with a suitable practical osmolality ( Figure 5).
- the osmolality of the poloxamer solution was also measured by freezing point depression method or vapor pressure methods.
- the practical osmolality of the formulation is measured using commercially available osmometers and the value is confirmed by the hemolysis assay.
- Table 4 shows a comparison of osmolality as determined by the serial dilution cell- based assay and a direct measurement using freezing point depression or vapor pressure methods.
- the serial dilution method is predictive of practical osmolality that is compatible with the sinonasal environment.
- b Hemolysis Index is defined as the 540 nm Absorbance ratio of sample:0.9% saline
- useful formulations also include one or more pH adjusting agents or buffering agents.
- Suitable pH adjusting agents or buffers include, but are not limited to acetate, bicarbonate, ammonium chloride, citrate, phosphate, pharmaceutically acceptable salts thereof and combinations or mixtures thereof.
- the amount of buffer included in the gel formulations are an amount such that the pH of the gel formulation does not interfere with the body's natural buffering system and/or the osmolarity of the sinonasal fluids.
- the pH of a formulation described herein is between about 3.0, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, or 7.0 and about 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 11.0, or 12.0. In some embodiments, the pH of a formulation described herein is between about 3.0 and about 12.0. In some embodiments, the pH of a formulation described herein is between about 3.0 and about 10.0. In some embodiments, the pH of a formulation described herein is between about 3.5 and about 8.5. In some embodiments, the pH of a formulation described herein is between about 4.0 and about 8.0. In some embodiments, the pH of a formulation described herein is between about 4.5 and about 8.0.
- the pH of a formulation described herein is between about 5.5 and about 8.0. In some embodiments, the pH of a formulation described herein is between about 6.5 and about 8.0. In some embodiments, the pH of a formulation described herein is between about 7.0 and about 7.8. In some embodiments, the pH of a formulation described herein is between about 7.0 and about 7.6. In some embodiments, the pH of a formulation described herein is between about 7.4 and about 7.8.
- the formulations described herein have a pH and/or practical osmolarity as described herein, and have a concentration of active pharmaceutical ingredient between about 1 ⁇ and about 10 ⁇ , between about 1 mM and about 100 mM, between about 0.1 mM and about 100 mM, or betwen about 0.1 mM and about 100 nM.
- the formulations described herein have a pH and/or practical osmolarity as described herein, and have a concentration of active pharmaceutical ingredient between about 0.01% - about 40%, between about 0.01% - about 20%, between about 0.01% - about 10%, between about 0.01% - about 7.5%, between about 0.01% - 6%, between about 0.01 - 5%, between about 0.1% - about 40%, between about 0.1% - about 30%, between about 0.1% - about 20%, between about 0.1 - about 10%, or between about 0.1 - about 6% of the active ingredient by weight of the formulation.
- formulations described herein comprise between about
- formulations described herein comprise between about 0.01% - 30% of the active ingredient by weight of the formulation. In some embodiments, formulations described herein comprise between about 0.01% - 20% of the active ingredient by weight of the formulation. In some embodiments, formulations described herein comprise between about 0.01% - 10% of the active ingredient by weight of the formulation.
- the formulations described herein have a pH and/or practical osmolarity as described herein, and have a concentration of active pharmaceutical ingredient between about 1 ⁇ g/mL and about 500 g/mL, between about 1 ⁇ g/mL and about 250 ⁇ g/mL, between about 1 ⁇ g and about 100 ⁇ g/mL, between about 1 ⁇ g/mL and about 50 ⁇ g/mL, or between about 1 ⁇ g/mL and about 20 ⁇ g/mL of the active agent by volume of the formulation.
- any formulation described herein comprises multiparticulates, i.e., a plurality of particle sizes (e.g., micronized particles, nano-sized particles, non-sized particles, colloidal particles); i.e, the formulation is a multiparticulate formulation.
- any formulation described herein comprises one or more multiparticulate (e.g., micronized) therapeutic agents.
- any formulation described herein comprises micronized therapeutic agents.
- Micronization is a process of reducing the average diameter of particles of a solid material.
- the average diameter of particles in a micronized solid is from about 0.5 ⁇ to about 500 ⁇ .
- the average diameter of particles in a micronized solid is from about 1 ⁇ to about 200 ⁇ .
- the average diameter of particles in a micronized solid is from about 2 ⁇ to about 100 ⁇ .
- the average diameter of particles in a micronized solid is from about 3 ⁇ to about 50 ⁇ .
- the use of multiparticulates of active agent allows for extended and/or sustained release of the active agent from any formulation described herein compared to a formulation comprising non-multiparticulate or a water-soluble active agent.
- the micronized active agent particles upon administration of a sustained release formulation comprising micronized active agent to an individual in need thereof, serve as a depot for further extended release of the active agent even after the gel has eroded. In some of such embodiments, the micronized particles remain adhered to sinusoidal and/or nasal and/or nasopharyngeal surfaces. Accordingly, in some
- sustained release sinonasal formulations suitable for methods described herein comprise substantially high concentrations of micronized active agent.
- sustained release sinonasal and/or nasopharyngeal formulations are suspensions comprising micronized active agents.
- any particle in any formulation described herein is a coated or uncoated particle (e.g., a coated micronized particle, nano-particle) and/or a microsphere and/or a liposomal particle.
- Particle size reduction techniques include, by way of example, grinding, milling (e.g., air-attrition milling (jet milling), ball milling), coacervation, complex coacervation, high pressure homogenization, spray drying and/or supercritical fluid crystallization.
- particles are sized by mechanical impact (e.g., by hammer mills, ball mill and/or pin mills).
- particles are sized via fluid energy (e.g., by spiral jet mills, loop jet mills, and/or fluidized bed jet mills).
- formulations described herein comprise crystalline particles and/or isotropic particles. In some embodiments, formulations described herein comprise amorphous particles and/or anisotropic particles. In some embodiments, formulations described herein comprise therapeutic agent particles wherein the therapeutic agent is a free base, or a salt, or a prodrug of a therapeutic agent, or any combination thereof.
- compositions comprising multiparticulate (e.g., micronized) active agents provide extended release over a longer period of time compared to compositions comprising non-particulate and/or water soluble active agents.
- the multiparticulate and/or less water-soluble active agent provides a steady supply (e.g., +/- 20%) of active agent via slow degradation and serves as a depot for the active agent; such a depot effect increases residence time of the active agent in the sinusoidal or nasal or naospharynx structures or cavities.
- selection of an appropriate particle size of the active agent (e.g., micronized active agent) and solubility of the active agent is water, in combination with the amount of thermoreversible polymer component in the composition, provides tunable extended release characteristics that allow for release of an active agent over a period of hours, days, weeks or months.
- the release characteristics of an active agent from a formulation described herein are tuned by modifying the solubility of the active agent in biological and/or aqueous media.
- One approach to extend release of an active agent is to desolubilize the soluble active agent.
- Solubility of the drug in biological and/or aqueous fluids is modified by selection of a pharmacologically acceptable salt that is insoluble or has a lower solubility than the drug alone or a different salt of the drug.
- solubility of the drug in biological and/or aqueous fluids is modified by selection of crystalline salt forms (polymorphs) that are insoluble or have lower solubility than other salt forms or the drug alone.
- a soluble drug is rendered insoluble or less soluble in biological and/or aqueous fluids by exchanging the counterion from a Group I metal ion (e.g., sodium or potassium), to a counterion from group II of the periodic table (e.g., calcium or magnesium) or any other polyvalent cation (e.g., iron, zinc, barium, cesium or the like).
- a Group I metal ion e.g., sodium or potassium
- group II of the periodic table e.g., calcium or magnesium
- any other polyvalent cation e.g., iron, zinc, barium, cesium or the like.
- an oligonucleotide anionic drug e.g., alicaforsen
- a protein e.g., insulin
- a zinc salt thereof is rendered insoluble or less soluble in biological and/or aqueous fluids by formation of a zinc salt thereof.
- a soluble drug is rendered insoluble or less soluble in biological and/or aqueous fluids by formulating at or above the pKa of at least one of the amine moieties.
- a formulation at a pH >5 reduces the solubility of the drug in biological and/or aqueous fluids.
- meclizine is insoluble in water with two amine groups (pKa of ⁇ 5 and 9), however it is readily solubilized in a poloxamer formulation when the pH of the solution is maintained below a pH of 5.5, and it is insoluble in a poloxamer formulation above a pH of 6.
- an active agent is a cationic drug (e.g., an agent bearing at least one amine moiety with a pKa ⁇ 5)
- a poloxamer gel formulation at a pH of 4.5 has a lower mean dissolution time (MDT) compared to a poloxamer formulation at a pH of 7.4.
- modifying the solubility of the active agent can also have an effect on the properties of the thermoreversible gel.
- amitriptyline is water soluble (greater than 100 mg/mL) and increases the gelation temperature of a poloxamer formulation. Reducing the solubility of amitriptyline (e.g., by formation of a prodrug) allows for tuning of the gelation temperature of a poloxamer formulation.
- cationic drugs are rendered insoluble or less soluble in biological and/or aqueous media by exchanging the salt of such a drug from a mineral acid salt (e.g., hydrochloric acid or sulfuric acid salts) to a salt of a small to medium sized organic acid (e.g., a citrate, maleate, nicotinate, or besylate salt or the like).
- a mineral acid salt e.g., hydrochloric acid or sulfuric acid salts
- a salt of a small to medium sized organic acid e.g., a citrate, maleate, nicotinate, or besylate salt or the like.
- dexamethasone acetate is less soluble than dexamethasone hydrochloride in biological and/or aqueous fluids.
- a water soluble active agent has a solubility of > 10 mg/ mL.
- An active agent that has been rendered less soluble or insoluble in aqueous and/or biological media has a water solubility of less than 10 mg/niL, less than lmg/mL or less than O. lmg/mL.
- the release profile of an active agent and/or any salts thereof is compared using in vitro and in vivo procedures described herein.
- a second approach for controlling the dissolution and/or release profile of an active agent is to form a complex of an active agent with a complexation agent that hinders dissolution of the active agent in biological and/or aqueous media.
- complexation agents include and are not limited to cryptands (e.g., [2.2.2]cryptand, diaza- 18-crown-6), cyclodextrins, crown ethers (e.g., 12-crown-4, 15-crown-5, 18-crown-6, dibenzo-18-crown-6 or the like), or the like.
- anionic active agents cationic (e.g., amine based) active agents and zwitterionic active agents are rendered insoluble or less soluble in biological and/or aqueous media by complexation with polymers (e.g., hyaluronic acid), insoluble organic compounds (e.g., surfactants such as phospholipids), or polyvalent metal ions (e.g., multimeric complexes with cesium, calcium, magnesium, iron, zinc, or the like).
- polymers e.g., hyaluronic acid
- insoluble organic compounds e.g., surfactants such as phospholipids
- polyvalent metal ions e.g., multimeric complexes with cesium, calcium, magnesium, iron, zinc, or the like.
- complex coacervation of proteins e.g., insulin
- bovine serum albumin (BSA) or gelatin modifies the dissolution and/or release profile of a protein from a formulation described herein.
- Yet another approach to tune the release profile of an active agent from a formulation described herein is to complex a salt or free base of an active agent with a polyelectrolyte (e.g., poly(sodium styrene sulfonate), polyacrylic acid, polyamines or the like).
- a polyelectrolyte e.g., poly(sodium styrene sulfonate), polyacrylic acid, polyamines or the like.
- the ionic interactions between the polyelectrolyte and the salt or free base of the active agent modify the dissolution characteristics of the active agent in biological and/or aqueous fluids.
- solubility of genetic material in biological and/or aqueous media is modified by addition of cationic polymers and/or formation of cationic micelles.
- the release profile of an active agent and a complex thereof is compared using in vitro and in vivo procedures described herein.
- a further approach to extend the release profile of an active agent from a formulation described herein is to use prodrugs of an active agent.
- An active agent anionic, cationic, zwitterionic or neutral
- An active agent is rendered insoluble or less soluble in biological and/or aqueous media by formation of a prodrug that is insoluble or less soluble in biological and/or aqueous media than the drug alone.
- prodrugs are formed by covalent attachment of a moiety (e.g., an ester, or amide of a bulky or water insoluble group such as benzoic acid, amines, fatty acids, cyclic or aromatic acids or alcohols, polymeric chains, or the like) to the parent drug.
- the release profile of an active agent and a prodrug thereof is compared using in vitro and in vivo procedures described herein.
- a further approach to tuning the dissolution properties and/or release profile of an active agent is to coat particles of the active agent with certain controlled release excipients (e.g., hydroxypropylmethyl cellulose, carboxymethylcellulose or the like).
- controlled release excipients e.g., hydroxypropylmethyl cellulose, carboxymethylcellulose or the like.
- an active agent is micronized and the micronized particles are coated with controlled release excipients; the coated active agent particulates are then formulated in any of the compositions described herein.
- the release profile of an active agent is tuned by changing the concentration of an active agent in the formulation. At increased concentration of an active agent, a) initial drug levels reached in the sinonasal cavity are high and b) there is an increase in the duration of exposure.
- Figure 3 illustrates the dose proportionality effect in vitro in a release kinetic assay in which increasing the drug concentration is associated with an increase in the mean dissolution time. An increase in active agent concentration in the formulation prolongs residence time and/or MDT of the active agent in the sinonasal cavitites.
- the MDT for an active agent from a formulation described herein is from about 30 hours to about 48 hours. In some embodiments, the MDT for an active agent from a formulation described herein is from about 30 hours to about 96 hours.
- a linear relationship between the formulations mean dissolution time (MDT) and the P407 (P407) concentration indicates that the active agent is released due to the erosion of the polymer gel (poloxamer) and not via diffusion.
- a non-linear relationship indicates release of active agent via a combination of diffusion and/or polymer gel degradation.
- the MDT is inversely proportional to the release rate of an active agent from a composition described herein.
- the released active agent is optionally fitted to the Korsmeyer-Peppas equation:
- MDT mean dissolution time
- the MDT for an active agent from a formulation described herein is from about 30 hours to about 1 week. In some embodiments, the MDT for a formulation described herein is from about 1 week to about 6 weeks.
- the mean residence time (MRT) for an active agent in a formulation described herein is from about 20 hours to about 48 hours. In some embodiments, the mean residence time (MRT) for an active agent in a formulation described herein is from about 20 hours to about 48 hours. In some
- the MRT for an active agent from a formulation described herein is from about 20 hours to about 96 hours. In some embodiments, the MRT for an active agent from a formulation described herein is from about 20 hours to about 1 week. In some embodiments, the MRT for an active agent from a formulation described herein is from about 1 week to about 6 weeks.
- the gel strength and concentration of the active agent affects release kinetics (e.g., mean dissolution time) of an active agent from the composition. For example, at low poloxamer concentration, elimination rate is accelerated (Mean Dissolution time (MDT) is lower).
- MDT Mel Dissolution time
- Figure 4 illustrates in vitro mean dissolution time of high versus low solubility drug substances and solution versus gel formulations.
- the MDT for poloxamer from a formulation described herein is at least 6 hours. In some embodiments, the MDT for poloxamer from a formulation described herein is at least 10 hours. In some embodiments, the MDT for poloxamer from a formulation described herein is at least 24, 48, 60, 100, 150, 200 or 250 hours. The MDT is determined using techniques described herein in, for example, Example 6.
- the polymer concentration and concentration of the active agent affects release kinetics (e.g., mean dissolution time) of an active agent from the composition.
- release kinetics e.g., mean dissolution time
- MDT Mel Dissolution time
- the formulation is washed away with the sinonasal fluids.
- high poloxamer concentration e.g., at poloxamer concentration between about 45% and about 75% by weight of the composition
- the formulation forms a thickened liquid and coats the target structures (MDT is higher).
- the Mean Residence Time (MRT) of an active agent in the sinonasal cavity for any formulation described herein is between about 5, 7, 10, 15, 20, 24, 36, 48, 60, 70 or 80 hours and about 100, 200, 300, 400, 500 or 600 hours.
- a composition described herein is a solution of
- microparticulates or micronized active agent and is substantially free of thermoreversible polymer components.
- the composition provides essentially immediate release of an active agent.
- microparticulates or micronized active agent that is substantially free of thermoreversible polymer components provides intermediate sustained release of active agent.
- a formulation comprising microparticulates or micronized active agent and a thermoreversible polymer provides an extended sustained release of active agent.
- immediate release of an active agent refers to substantially complete release of an active agent from the formulation in less than about 5 hours.
- sustained release refers to extended release of an active agent from a formulation such as, for example, a sustained release of active agent over at least 2, 3, 5, 7, 14, 21, 28 days, or at least 1, 2, 3, 4, 5 or 6 months or 1 year.
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 1 day. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 2 days.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 2 days. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 3 days.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 4 days. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 5 days.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 6 days. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 7 days.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 8 days. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 9 days.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 10 days. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 2 weeks.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 3 weeks. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 4 weeks.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 5 weeks. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 7 days.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 6 weeks. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 7 weeks.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 8 weeks. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 3 months.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 4 months. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 5 months.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 6 months. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 7 months.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 8 months. In some embodiments, intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 10 months.
- an active agent e.g., a corticosteroid, an antibiotic
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations provided herein provide sustained release of an active agent (e.g., a corticosteroid, an antibiotic) for a period of at least 12 months.
- an active agent e.g., a corticosteroid, an antibiotic
- a suspension of microparticulates or micronized active agent provides intermediate sustained release or extended sustained release.
- a composition comprising a thermoreversible polymer and microparticulate or micronized active agent provides intermediate sustained release or extended sustained release.
- a solution of an active agent provides immediate release or intermediate sustained release.
- thermoreversible gel described herein advantageously allows for substantially uniform distribution of an active agent throughout the sinonasal cavities.
- solutions of dexamethasone that do not contain thermoreversible polymers provide uneven distribution (large gradient, variability in drug exposure) of active agents in the sinonasal region.
- the pharmacokinetic profile of active agents that are administered sinonasally is dependent on the nature of the vehicle (for example, aqueous solution comprising a thermoreversible polymer versus aqueous solution that does not contain a thermoreversible polymer).
- the pharmacokinetic profile of active agents that are administered sinonasally also depends on the physicochemical properties of the active agent as described above.
- a combination of an appropriate thermoreversible polymer vehicle and physicochemical properties of a drug provides an optimized release profile.
- a 17% Poloxamer 407 formulation when either dexamethasone or methylprednisolone is present as a water soluble salt, i.e.
- MDT values are about 3h.
- the MDT values of water insoluble forms of dexamethasone and methylprednisolone range from 40 to 71 h.
- a DSP aqueous solution has a MDT of 0.3h whereas a micronized DEX suspension in water has a MDT value of 44h.
- dexamethasone formulated in poloxamer 407 allow for tunable pharmacokinetics.
- DSP dexamethasone sodium phosphate
- DSP soluble form of dexamethasone
- DSP water insoluble form of dexamethasone
- DA Dexamethasone acetate
- the release profile of methylprednisolone is tunable via the use of soluble methylprednisolone sodium (MPS) and water insoluble methyprednisolone (MP) forms.
- MPS soluble methylprednisolone sodium
- MP water insoluble methyprednisolone
- the use of the more soluble Methylprednisolone sodium in P407 formulations described herein provides release of methylprednisolone from the gel for a shorter period of time compared to the use of less soluble MP in a P407 formulation described herein.
- the nature and the composition of the vehicle and the degree of aqueous solubility of the drug present in the formulation affects pharmacokinetic parameters such as the mean residence time and/or exposure in the sinonasal cavities.
- the concentration of the drug in the sinonasal fluids stays at or about the therapeutic dose for an extended period of time (e.g., one day, 2 days, 3 days, 4 days, 5 days, 6 days, or 1 week, 3 weeks, 6 weeks, 2 months).
- the steady state concentration of active agent released from a controlled release formulation described herein is about 5 to about 20 times the steady state concentration of an active agent released from a formulation that is not a controlled release formulation.
- the steady state concentration of active agent released from a controlled release formulation described herein is about 20 to about 50 times the steady state concentration of an active agent released from a formulation that is not a controlled release formulation.
- any formulation described herein provides extended release of an active agent in the sinonasal cavities or in the vicinity of sinonasal sites and/or nasal sites and/or nasopharyngeal sites for at least 7 days, at least 10 days, at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 12 weeks or at least 16 weeks.
- compositions that include at least one active agent and a pharmaceutically acceptable diluent(s), excipient(s), or carrier(s).
- a sinonasal formulation described herein comprises between about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or 55% and about 0.5%, 1%, 5%, 10%, 15%, 20% 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80% or 89% of a viscosity enhancing polymer.
- a viscosity enhancing polymer is a thermosensitive polymer.
- a viscosity enhancing polymer is a pH sensitive polymer.
- a viscosity enhancing polymer is sensitive to concentration of ions (e.g., in some instances, alginates gel in presence of Ca +2 ions).
- sinonasal formulation described herein comprises between about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or 55% and about 25%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% of a thermoreversible polymer.
- the resulting formulation is a thermoreversible gel, but it need not be thermoreversible; that is, depending on the amount of thermoreversible polymer, the resulting gel may be thermoreversible or not thermoreversible.
- the classification "thermoreversible polymer” refers to polymers that are capable of forming thermoreversible gels in the range 5-42 degrees Celsius.
- thermoreversible gels when incorporated into aqueous solutions. These polymers have the ability to change from the liquid state to the gel state at temperatures close to body temperture, therefore allowing useful formulations that are applied to the targeted sinonasal structure(s).
- the liquid state-to-gel state phase transition (gelation temperature) is dependent on the polymer concentration, buffer concentration and the ingredients in the solution.
- a thermoreversible gel suitable for compositions described herein is an aqueous gel comprising of a polymer of polyoxypropylene and
- Poloxamer is a synthetic block polymer of ethylene oxide and propylene oxide.
- Poloxamer 407 also known as PF-127, P407, Pluronic-127 is a theroreversible polymer composed of polyoxyethylene-polyoxypropylene copolymers.
- Other poloxamers include 124, 188 (F-68 grade), 237 (F-87 grade), and 338 (F-108 grade).
- Aqueous solutions of poloxamers are stable in the presence of acids, alkalis, and metal ions.
- PF-127 (or P407) is a commercially available polyoxyethylene-polyoxypropylene triblock copolymer, with an average molar mass of 13,000.
- the polymer can be further purified by suitable methods that will enhance gelation properties of the polymer. It contains approximately 70% ethylene oxide, which accounts for its hydrophilicity. It is one of the series of poloxamer ABA block copolymers, whose members share the chemical formula shown below.
- Poloxamers are available in several types, and with varying molecular weights ranging from about 2000 to about 15000.
- the a-hydro-co-hydroxypoly(oxyethylene) a poly(oxypropylene) b poly(oxyethylene) a block copolymers comprise varying ratios of a b as shown below:
- a thermoreversible gel formulation described herein comprises a poloxamer.
- a thermoreversible gel formulation described herein comprises P407.
- poloxamers e.g., P407
- P407 have good solubilizing capacity, low toxicity, and are compatible with sinonasal surfaces.
- the thermoreversible gel comprises a PEG-PLGA- PEG triblock copolymer (Jeong etal, Nature (1997), 388:860-2; Jeong etal, J. Control. Release (2000), 63 : 155-63; Jeong etal, Adv. Drug Delivery Rev. (2002), 54:37-51).
- the polymer exhibits sol-gel behavior over a concentration of about 5% w/w to about 40% w/w.
- the lactide/glycolide molar ratio in the PLGA copolymer ranges from about 1 : 1 to about 20: 1.
- the resulting coploymers are soluble in water and form a free-flowing liquid at room temperature, but form a gel at body temperature.
- ReGel® is a tradename of MacroMed Incorporated for a class of low molecular weight, biodegradable block copolymers having reverse thermal gelation properties as described in U.S. Pat. Nos. 6,004,573, 6, 117949, 6,201,072, and 6,287,588. It also includes biodegradable polymeric drug carriers disclosed in pending U.S. patent application Ser. Nos. 09/906,041, 09/559,799 and 10/919,603.
- the biodegradable drug carrier comprises ABA-type or BAB-type triblock copolymers or mixtures thereof, wherein the A-blocks are relatively hydrophobic and comprise biodegradable polyesters or poly(orthoester)s, and the B-blocks are relatively hydrophilic and comprise polyethylene glycol (PEG), said copolymers having a hydrophobic content of between 50.1 to 83% by weight and a hydrophilic content of between 17 to 49.9% by weight, and an overall block copolymer molecular weight of between 2000 and 8000 Daltons.
- A-blocks are relatively hydrophobic and comprise biodegradable polyesters or poly(orthoester)s
- the B-blocks are relatively hydrophilic and comprise polyethylene glycol (PEG), said copolymers having a hydrophobic content of between 50.1 to 83% by weight and a hydrophilic content of between 17 to 49.9% by weight, and an overall block copolymer molecular weight of between 2000 and 8000 Daltons.
- thermoreversible polymers are useful depending upon the particular active agent, other pharmaceutical agent or excipients/additives used, and as such are considered to fall within the scope of the present disclosure.
- other commercially-available glycerin-based gels, glycerin-derived compounds, conjugated, or crosslinked gels, matrices, hydrogels, and polymers, as well as gelatins and their derivatives, alginates, and alginate-based gels, and even various native and synthetic hydrogel and hydrogel-derived compounds are all expected to be useful in the
- bioacceptable gels include, but are not limited to, alginate hydrogels SAF®-Gel (ConvaTec, Princeton, N.J.), Duoderm® Hydroactive Gel (ConvaTec), Nu-gel ⁇ (Johnson & Johnson Medical, Arlington, Tex.); Carrasyn®(V) Acemannan Hydrogel (Carrington Laboratories, Inc., Irving, Tex.); glycerin gels Elta® Hydrogel (Swiss-American Products, Inc., Dallas, Tex.), K-Y® Sterile (Johnson & Johnson), gelatin hydrogels, chitosan, silicon-base gels (e.g., Medgel®) or the like.
- thermoreversible and/or bioacceptable gels suitable for sinonasal compositions comprise acrylic acid-based polymers (e.g., Carbopol®), cellulose based polymers (e.g., hydroxypropylmethyl cellulose, carboxymethyl cellulose, or the like), alkyl aryl polyether alcohol-based polymer (e.g., Tyloxapol®), or the like.
- acrylic acid-based polymers e.g., Carbopol®
- cellulose based polymers e.g., hydroxypropylmethyl cellulose, carboxymethyl cellulose, or the like
- alkyl aryl polyether alcohol-based polymer e.g., Tyloxapol®
- any active composition described herein comprises purified thermoreversible polymer.
- any active composition described herein comprises fractionated a purified thermoreversible polymer composed of polyoxyethylene- polyoxypropylene copolymers.
- the thermoreversible polymer is a poloxamer.
- the purification of poloxamers is based on the removal of low molecular weight components (e.g., oligomers, unreacted material and/or other unwanted impurities that are produced during manufacturing or storage) and/or large molecular weight components (components from unwanted polymer-polymer reactions).
- the resulting purified product has a narrower PDI with approximately the same molecular weight as the original material.
- a purified poloxamer has better gelling characteristics (e.g., a lower Tgel for the same % poloxamer concentration while providing a higher viscosity in the gel state).
- a purified thermoreversible polymer has low polydispersity (i.e., a narrow distribution of molecular weights amongst the individual polymer chains therein).
- commercially available poloxamers contain certain impurities such as poly(oxyethylene) homopolymer and poly(oxyethylene)/poly(oxypropylene) diblock polymers due to the nature of the manner in which they are produced.
- the relative amounts of these byproducts increase as the molecular weights of the component blocks increase.
- byproducts may constitute from about 15 to about 50% by weight of the polymer depending upon the manufacturer, thereby resulting in high polydispersity.
- Example 24 illustrates a procedure for fractionation of P407 that reduces polydispersity in commercially available P407.
- super critical fluid extraction technique is used to fractionate polyoxyalkylene block copolymers. See, U.S. Pat. No. 5,567,859, the disclosure for fractionation of polymers described therein is incorported herein by reference.
- this technique lower molecular weight fractions in commercially purchased polymer are removed in a stream of CO 2 maintained at a pressure of 2200 pounds per square inch (psi) and a temperature of 40 °C, thereby providing purified polymer having low polydispersity.
- gel permeation chromoatography allows for isolation of fractions of polymers. See, European Patent Application WO 92/16484; the use of gel permeation chromatography to isolate a fraction of poloxamer having low polydispersity and saturation described therein is incorporated herein by reference.
- one or more of the blocks is purified prior to manufacture of the copolymer.
- purifying either the polyoxypropylene center block during synthesis of the copolymer, or the copolymer product itself allows for manufacture of purified poloxamers.
- fractionation of polyoxyalkylene block copolymers is acheived by batchwise removal of low molecular weight species using a salt extraction and liquid phase separation technique (See, U.S. Pat. No. 5,800,71 1, which process of purification of polymers described therein is incorporated herein by reference).
- Such fractionation produces polyoxyalkylene block copolymers (e.g., poloxamer 407, poloxamaer 188 or the like) having improved physical characteristics including increased gel strength, decreased polydispersity, higher average molecular weight, decreased gelling concentration and/or extended gel dissolution profiles compared to commercially available poloxamers (e.g., P407 NF grade from BASF).
- Other processes for purification and/or fractionation of polymers are described in, for example, US 6,977,045 and US 6,761,824 which processes are incorporated herein by reference.
- low molecular weight contaminants of polymers e.g., poloxamers
- poloxamers e.g., poloxamers
- the use of purified poloxamers in pharmaceutical formulations described herein reduces such in vivo side effects.
- formulations comprising purified poly(oxyethylene)/poly(oxypropylene) triblock polymers that are substantially free of the poly(oxyethylene) homopolymers and/or poly(oxypropylene)/poly(oxyethylene) diblock byproducts, thereby narrowing the molecular weight distribution of block copolymers, (i.e., providing low polydispersity).
- such purified poly(oxyethylene)/poly(oxypropylene) triblock polymers allow for formulation of active compositions that comprise lower concentrations of the poly(oxyethylene)/poly(oxypropylene) triblock polymers compared to active compositions that comprise non-fractionated
- poly(oxyethylene)/poly(oxypropylene) triblock polymers are poly(oxyethylene)/poly(oxypropylene) triblock polymers.
- compositions comprising lower concentrations of fractionated poly(oxyethylene)/poly(oxypropylene) triblock polymers (e.g., poloxamers) retain gelation properties (e.g., gelation between about 15 °C and about 42 °C) and sustained release characteristics (e.g., sustained release of dexamethasone over at least 3 days, 5 days or 7 days) despite having a lower concentration of the poly(oxyethylene)/poly(oxypropylene) triblock polymer (e.g., poloxamer).
- gelation properties e.g., gelation between about 15 °C and about 42 °C
- sustained release characteristics e.g., sustained release of dexamethasone over at least 3 days, 5 days or 7 days
- dexamethasone and lower concentrations of fractionated P407 e.g., between about 5% to about 14% P407
- pharmaceutical formulations described herein comprise gelation temperature modifying agents.
- a "gelation temperature modifying agent” or a “gel temperature modifying agent” is an additive added to any formulation described herein, and changes the gelation temperature of the formulation such that the gel temperature of the formulation is maintained between about 5 °C and about 42 °C.
- a gel temperature modifying agent increases or decreases the gelation temperature of any formulation described herein such that the formulation maintains a gelation temperature of between about 5 °C and about 42 °C.
- a gel temperature modifying agent increases or decreases the gelation temperature of any formulation described herein such that the formulation maintains a gelation temperature of between about 14 °C and about 42 °C.
- a gel temperature modifying agent is a gel temperature increasing agent.
- a formulation comprising a
- thermoreversible polymer has a gelation temperature below 14 °C
- a gel temperature increasing agent e.g., PI 88, P388, cyclodextrin, carboxymethyl cellulose, hyaluronic acid, Carbopol®
- a gel temperature modifying agent is a gel temperature decreasing agent.
- thermoreversible polymer has a gelation temperature above 42 °C
- addition of a gel temperature decreasing agent e.g., PI 88, P388, cyclodextrin, carboxymethyl cellulose, hyaluronic acid, Carbopol®
- a gel temperature decreasing agent e.g., PI 88, P388, cyclodextrin, carboxymethyl cellulose, hyaluronic acid, Carbopol®
- a gel temperature modifying agent is a pH sensitive polymer (e.g., chitosan).
- a gel temperature modifiying agent is a
- a gel temperature modifying agent is an ion-sensitive polymer (e.g., alginates gel in the presence of calcium ions).
- a gel temperature modifying agent is an acrylic acid-based polymer (e.g., Carbopol®).
- a gel temperature modifiying agent is a cellulose based polymer (e.g., hydroxypropylmethyl cellulose, carboxymethyl cellulose, or the like).
- a gel temperature modifying agent is an alkyl aryl polyether alcohol- based polymer (e.g., Tyloxapol®)
- a gel temperature modifiying agent is a poloxamer.
- a poloxamer By way of example, addition of not more than about 5% poloxamer 188 to a formulation comprising about 16% P407 increases the gelation temperature of a 16% P407 formulation by about 5 °C.
- a pharmaceutical formulation described herein is a liquid at about room temperature.
- the pharmaceutical formulation is characterized by a phase transition between about room temperature and about body temperature (including an individual with a serious fever, e.g., up to about 42 °C).
- the phase transition occurs between at least about 1 °C below body temperature and body temperature, between at least about 2 °C below body temperature and body temperature, between at least about 3 °C below body temperture and body temperature, between at least about 4 °C below body temperature and body temperature, between at least about 6 °C below body temperature and body temperature, between at least about 8 °C below body temperature and body temperature, between at least about 10 °C below body temperature and body temperature, between at least about 15 °C below body temperature and body temperature, or between at least about 20 °C below body temperature and body temperature.
- a formulation described herein has a gelation temperature of between about 5 °C, 10 °C, 14 °C, 15 °C, 16 °C, 17 °C, 18 °C, 19 °C, or 20 °C, and about 25 °C, 28 °C, 30 °C, 33 °C, 35 °C , 37 °C , 40 °C or 42 °C.
- a formulation described herein has a gelation temperature of between about 15 °C, 16 °C, 17 °C, 18 °C, 19 °C, or 20 °C, and about 25 °C, 28 °C, 30 °C , 33 °C, 35 °C , 37 °C , 40 °C or 42 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 5 °C and about 42 °C. . In some embodiments, a formulation described herein has a gelation temperature of between about 5 °C and about 35 °C. .
- a formulation described herein has a gelation temperature of between about 5 °C and about 25 °C. . In some embodiments, a formulation described herein has a gelation temperature of between about 5 °C and about 20 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 10 °C and about 42 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 14 °C and about 42 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 14 °C and about 40 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 15 °C and about 40 °C.
- a formulation described herein has a gelation temperature of between about 14 °C and about 37 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 14 °C and about 35 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 16 °C and about 35 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 18 °C and about 35 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 20 °C and about 42 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 15 °C and about 37 °C.
- a formulation described herein has a gelation temperature of between about 20 °C and about 37 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 15 °C and about 35 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 20 °C and about 35 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 19 °C and about 35 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 17 °C and about 35 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 20 °C and about 30 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 20 °C and about 28 °C. In some embodiments, a formulation described herein has a gelation temperature of between about 20 °C and about 25 °C.
- methods of solubilization include adding the required amount of polymer to the amount of water to be used at reduced tempertures. Generally after wetting the polymer by shaking, the mixture is capped and placed in a cold chamber or in a thermostatic container at about 0-10 °C in order to dissolve the polymer. In some embodiments, the dissolution is carried out a temperature between about 10 °C and about 20 °C. The mixture is stirred or shaken to bring about a more rapid dissolution of the thermoreversible polymer. In some instances the active agent and/or other pharmaceutically active agent is suspended if it is insoluble in water. The pH/osmolarity of the formulation is modulated by the addition of appropriate buffering agents.
- a formulation described herein contains a thermoreversible polymer sufficient to provide a viscosity of between about 10,000 and about 1,000,000 centipoise. In some embodiments, a formulation described herein contains a
- thermoreversible polymer sufficient to provide a viscosity of between about 50,000 and about 1,000,000 centipoise.
- a formulation described herein contains a thermoreversible polymer sufficient to provide a viscosity of between about 150,000 and about 1,000,000 centipoise.
- a formulation described herein contains a thermosetting polymer sufficient to provide a viscosity of between about 50,000 and about 600,000 centipoise.
- a formulation described herein contains a thermoreversible polymer sufficient to provide a viscosity of between about 100,000 and about 500,000 centipoise.
- a formulation described herein contains a thermoreversible polymer sufficient to provide a viscosity of between about 150,000 and about 400,000 centipoise.
- a thermoreversible polymer concentration of about 15.5% in a composition described herein provides an apparent viscosity of about
- thermoreversible polymer concentration of about 16% in a composition described herein provides an apparent viscosity of about 360,000 cP.
- thermoreversible polymer concentration of about 17% in a composition described herein provides an apparent viscosity viscosity of about 480,000 cP.
- the formulations described herein are low viscosity formulations at body temperature.
- a low viscosity formulation described herein provides an apparent viscosity of from about 100 cP to about 10,000 cP.
- use of a higher concentration of active agent results in formulations having higher viscosity compared to formulations have lower concentration of active agents.
- increase in concentration of drug in the formulation, and use of purified poloxamer allows for use of lower concentrations of thermoreversible polymer by weight of the formulation.
- the viscosity is measured at a shear rate of 0.31 s "1 using a cone/plate viscometer ( Brookfield DVII + Pro viscometer with a CP50 spindle at 0.08 rpm as a reference).
- formulations described herein comprise buffers.
- a buffer such as acetate or citrate buffer at slightly acidic pH.
- the buffer is a sodium acetate buffer having a pH of about 4.5 to about 6.5.
- the buffer is a sodium citrate buffer having a pH of about 5.0 to about 8.0, or about 5.5 to about 7.0.
- the buffer used is tris(hydroxymethyl)aminomethane, bicarbonate, carbonate or phosphate at slightly basic pH.
- the buffer is a sodium bicarbonate buffer having a pH of about 6.5 to about 8.5, or about 7.0 to about 8.0.
- the buffer is a sodium phosphate dibasic buffer having a pH of about 6.0 to about 9.0.
- the concentration of the buffer component is adjusted to bring the practial osmolarity of any formulation described herein within an acceptable range.
- the solvent in a formulation described herein, is water.
- a formulation described herein comprises a mixture of solvents (e.g., a mixture of water and an alcohol, or the like).
- the solvent in a formulation described herein the solvent is a mixture of ethanol and water.
- a formulation described herein further comprises additional sinonasal cavity -compatible excipients.
- additional excipients include agents for imaging and/or visualization as described herein.
- Other additional excipients include mucoadhesives, e.g., hyaluronic acid, (including and not limited to Hyalastine®,
- Hyalectin®, Hyaloftil®), and/or partial esters and/or salts thereof e.g., barium salt of hyaluronic acid, or any other salt of hyaluronic acid described in WO/1998/017285, salts described therein are incorported herein by reference.
- Other examples of mucoadhesives include cellulose based polymers, polynivyl polymers, PEG, chitosan, polyacrylates (e.g., Carbopol® polymers), Eudragit and the like.
- sinonasal compositions described herein comprise penetration enhancers such as, for example, hyaluronidase (e.g., PH-20 (Halzoyme)), alkyl saccharides (e.g., dodecyl maltoside, or the like), or any other excipient that modulates release profile and/or stabilty and/or permeability and/or drug uptake and/or bioavailability and/or toxicity and/or immunogenicity and/or gelation characteristics of any formulation described herein. Additional excipients are described in U.S. Appl. Nos.
- the formulations described herein are administered via injection or catheter or cannula in one or more sinonasal cavities or in the vicinity of one or more sinonasal cavities.
- the formulations described herein are administered onto or in the vicinity of a sinonasal strucuture (e.g., a deformed turbinate, a sinonasal polyp) via injection or perfusion or catheter before and/or during and/or after sinonasal surgery.
- a sinonasal strucuture e.g., a deformed turbinate, a sinonasal polyp
- the sinusoidal cavities including the ethmoid, maxillary, sphenoid and/or frontal sinusoidal cavities and/or other sinonasal sites and/or
- nasopharyngeal sites will occur via direct injection in the cavity (e.g., by use of an endoscope in the nasal passage) and/or the vicinity of the sites.
- delivery of intrasinusoidal compositions described herein is achieved via commercially available catheters, optionally in conjunction with balloon rhinoplasty, or septoplasty.
- the sinusoidal sustained- release formulations are capable of being administered on or near a nasal polyp.
- the intrasinusoidal controlled release formulations are administered on or near the turbinate and/or site of surgical manipulation.
- the sinonasal controlled release formulation is applied via syringe and needle, wherein the needle is inserted through the sinonasal passages and guided to the area of surgery and/or infection and/or nasal polyps.
- sinonasal formulations described herein are administered as a nasal spray or a nasal salve. Nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism. In some other embodiments, sinonasal formulations described herein are administered via a nebulizer. In yet other embodiments, sinonasal formulations described herein are adminstered as an irrigant.
- liposomes e.g., a self-assembling hydrogel displaying properties that also allow the gel to function as an absorption enhancer (e.g., a gel comprising hyaluronic acid); including instances in which the penetration enhancer is a surfactant comprising an alkyl-glycoside and/or a saccharide alkyl ester), other viscous media, paints, foams, in situ forming spongy materials, xerogels, actinic radiation curable gels, liposomes, solvent release gels, nanocapsules or nanospheres, and combinations thereof; further options or components include mucoadhesives, penetration enhancers, bioadhesives, antioxidants, surfactants, buffering
- thermoreversible gels or post-administration viscosity-enhancing options are also envisioned within the scope of embodiments presented herein, as well as alternative delivery systems, including pumps, microinjection devices and the like.
- a compositon disclosed herein is administered to an individual in need thereof once. In some embodiments, a compositon disclosed herein is administered to an individual in need thereof more than once.
- a composition is administered to an individual in need thereof depends on the discretion of a medical professional, the disorder, the severity of the disorder, and the individuals's response to the formulation.
- a formulation described herein is administered as prophylactically, therapeutically or as a chronic treatment over an extended perior of time.
- the administration of the active agent compounds may be given continuously; alternatively, the dose of drug being administered may be temporarily reduced or temporarily suspended for a certain length of time (i.e., a "drug holiday").
- the length of the drug holiday varies between 2 days and 1 year, including by way of example only, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, 35 days, 50 days, 70 days, 100 days, 120 days, 150 days, 180 days, 200 days, 250 days, 280 days, 300 days, 320 days, 350 days, and 365 days.
- the dose reduction during a drug holiday may be from 10%- 100%, including by way of example only 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, and 100%.
- a maintenance active agent dose is administered if necessary. Subsequently, the dosage or the frequency of administration, or both, is optionally reduced, as a function of the symptoms, to a level at which the improved disease, disorder or condition is retained. In certain embodiments, patients require intermittent treatment on a long-term basis upon any recurrence of symptoms.
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations described herein are manufactured as ready to use single component solutions that are administered to an individual in need thereof.
- intrasinusoidal and/or nasal and/or nasopharnygeal formulations described herein are manufactured as multi-component kits comprising dry-heat sterilized multiparticulate (e.g., micronized, nanoparticles, non-sized particles) active agent powder, a medium for reconstitution of the dry powder (e.g., sterile water or buffer or saline) and/or a solution comprising the thermoreversible polymer and a buffer.
- the dry powder is reconstituted with the sterile medium and/or the solution comprising the thermoreversible polymer and buffer just prior to administration of the sinonasal formulation to an individual in need thereof.
- Example 1 Preparation of a Thermoreversible Gel Dexamethasone Composition comprising micronized dexamethasone powder
- a 10-g batch of gel formulation containing 2.0% micronized dexamethasone is prepared. 13.8 mg of sodium phosphate dibasic dihydrate USP (Fisher Scientific.) + 3.1 mg of sodium phosphate monobasic monohydrate USP (Fisher Scientific.) + 74 mg of sodium chloride USP (Fisher Scientific.) is dissolved with 8.2g of sterile filtered DI water and the pH is adjusted to 7.4 with 1 M NaOH. The buffer solution is chilled down and 1.6 g of poloxamer 407 (BASF Corp., containing approximately 100 ppm of BHT) is sprinkled into the chilled PBS solution while mixing, solution is mixed until all the poloxamer is dissolved.
- poloxamer 407 BASF Corp., containing approximately 100 ppm of BHT
- the poloxamer is sterile filtered using a 33mm PVDF 0.22 ⁇ sterile syringe filter (Millipore Corp.) and delivered to 2 mL sterile glass vials (Wheaton) in an aseptic environment, the vials are closed with sterile butyl rubber stoppers (Kimble) and crimped sealed with 13 mm Al seals (Kimble).
- Examples 2-1 1 Formulations comprising amoxicillin, moxifloxacin, prednisolone, micronized ciprofloxacin hydrate, ofloxacin, levofloxacin, ceftriaxone, cefixime, azithromycin, and clarithromycin, respectively are prepared using the procedure described above in Example 1.
- Example 12 Preparation of a Thermoreversible Gel AM-101 Composition comprising NMDA receptor antagonist
- poloxamer 407 BASF Corp., containing approximately 100 ppm of BHT
- a chilled PBS solution while mixing, solution is mixed until all the poloxamer is dissolved.
- the poloxamer is sterile filtered using a 33mm PVDF 0.22 ⁇ sterile syringe filter (Millipore Corp.) and delivered to 2 mL sterile glass vials (Wheaton) in an aseptic environment, the vials are closed with sterile butyl rubber stoppers (Kimble) and crimped sealed with 13 mm Al seals (Kimble).
- micronized AM-101 is placed in separate clean depyrogenated vials, the vials are closed with sterile butyl rubber stoppers (Kimble) and crimped sealed with 13 mm Al seals (Kimble), vials are dry heat sterilized (Fisher Scientific Isotemp oven) at 140°C.
- 1 mL of the cold poloxamer solution is delivered to a vial containing 20 mg of sterile micronized AM-101 using a 21G needle (Becton Dickinson) attached to a 1 mL sterile syringe (Becton Dickinson), suspension mixed well by shaking to ensure homogeneity of the suspension.
- the suspension is withdrawn with the 21G syinge and the needle is switched to a 27 G needle for administration.
- a solution containing poloxamers is prepared as described above in Example 1 and is sterile filtered using a 33mm PVDF 0.22 ⁇ sterile syringe filter (Millipore Corp.) and delivered to 2 mL sterile glass vials (Wheaton) in an aseptic environment.
- the vials are closed with sterile butyl rubber stoppers (Kimble) and crimped sealed with 13 mm Al seals (Kimble).
- Example 14 Preparation of a Thermoreversible Gel Dexamethasone Composition comprising antihistamine
- a solution of poloxamer and PEG is prepared as described above and sterile filtered using a 33mm PVDF 0.22 ⁇ sterile syringe filter (Millipore Corp.) and delivered to 2 mL sterile glass vials (Wheaton) in an aseptic environment.
- the vials are closed with sterile butyl rubber stoppers (Kimble) and crimped sealed with 13 mm Al seals (Kimble).
- Example 15 Preparation of a Thermoreversible Gel Dexamethasone Composition comprising antifungal agent
- a solution comprising poloxamer (See example 24) and CMC is prepared as above and is sterile filtered using a 33mm PVDF 0.22 ⁇ sterile syringe filter (Millipore Corp.). 40 mg of micronized clotrimazole is added to the vials and the vials are sealed. The vials are autoclaved at 121 °C.
- HPLC analysis was performed using an Agilent 1200 equipped with a Luna CI 8(2) 3 ⁇ , lOOA, 250x4.6 mm column) using a 30-95 of solvent B ( solvent A 35%
- the dry heat sterilized dexamethasone is optionally mixed aseptically with a sterile- filtered poloxamer solution prior to administration.
- Example 17 Preparation of a Thermoreversible Gel Dexamethasone Composition
- Example 18 Preparation of a Thermoreversible Gel Composition comprising
- a 10-g batch of gel formulation containing 2.0% (ciprofloxacin and micronized dexamethasone) is prepared.
- 13.8 mg of sodium phosphate dibasic dihydrate USP (Fisher Scientific.) + 3.1 mg of sodium phosphate monobasic monohydrate USP (Fisher Scientific.) + 74 mg of sodium chloride USP (Fisher Scientific.) is dissolved with 8.2 g of sterile filtered DI water and the pH is adjusted to 7.4 with 1 M NaOH.
- the buffer solution is chilled down and 1.6 g of poloxamer 407 (BASF Corp., containing approximately 100 ppm of BHT) is sprinkled into the chilled PBS solution while mixing, solution is mixed until all the poloxamer is dissolved.
- the poloxamer is sterile filtered using a 33mm PVDF 0.22 ⁇ sterile syringe filter (Millipore Corp.) and delivered to 2 mL sterile glass vials (Wheaton) in an aseptic environment, the vials are closed with sterile butyl rubber stoppers (Kimble) and crimped sealed with 13 mm Al seals (Kimble). 20 mg of ciprofloxacin and micronized dexamethasone powders is placed in separate clean depyrogenated vials, the vials are closed with sterile butyl rubber stoppers (Kimble) and crimped sealed with 13 mm Al seals
- vials are dry heat sterilized (Fisher Scientific Isotemp oven) for 7 hours at 140°C.
- 1 mL of the cold poloxamer solution is delivered to a vial containing 20 mg of sterile ciprofloxacin and micronized dexamethasone using a 21G needle (Becton Dickinson) attached to a 1 mL sterile syringe (Becton Dickinson), suspension mixed well by shaking to ensure homogeneity of the suspension.
- the suspension is then withdrawn with the 21G syinge and the needle is switched to a 27 G needle for administration.
- a formulation comprising micronized dexamethasone and moxifloxacin is prepared according to Example 18 above. Fractionated poloxamer is prepared according to Example 24 described herein.
- Example 20 Effect of pH on degradation products for autoclaved 17% poloxamer 407NF/ 2% active agent in PBS buffer
- a stock solution of a 17% poloxamer 407/ 2% active agent is prepared by dissolving 351.4 mg of sodium chloride (Fisher Scientific), 302.1 mg of sodium phosphate dibasic anhydrous (Fisher Scientific), 122.1 mg of sodium phosphate monobasic anhydrous (Fisher Scientific) and an appropriate amount of an active agent with 79.3 g of sterile filtered DI water.
- the solution is cooled down in a ice chilled water bath and then 17.05 g of poloxamer 407NF (SPECTRUM CHEMICALS) is sprinkled into the cold solution while mixing. The mixture is further mixed until the poloxamer is completely dissolved. The pH for this solution is measured.
- a 2% solution of an active agent in PBS pH 7.3 is prepared by dissolving an appropriate amount of the active agent in the PBS buffer and QS to 10 g with PBS buffer.
- Appearance e.g., discoloration and/or precipitation
- HPLC analysis is performed using an Agilent 1200 equipped with a Luna CI 8(2) 3 ⁇ , lOOA, 250x4.6 mm column) using a 30-80 acetonitrile gradient (1-lOmin) of (water - acetonitrile mixture containing 0.05%TFA), for a total run of 15 minutes.
- Samples are diluted by taking 30 ⁇ . of sample and dissolved with 1.5mL of a 1 : 1 acetonitrile water mixture. Purity of the active agent in the autoclaved samples is recorded.
- Formulations comprising gentamicin, ciprofloxacin and micronized dexamethasone, prepared according to the procedure above, are tested using the above procedure to determine the effect of pH on degradation during the autoclaving step.
- Example 21 Effect of buffer type on the degradation products for formulations containing poloxamer 407NF after heat sterilization (autoclaving).
- a TRIS buffer is made by dissolving 377.8 mg of sodium chloride (Fisher
- a series of formulations is prepared with the above stock solution.
- An appropriate amount of active agent (or salt or prodrug thereof) and/or active agent as micronized/coated/liposomal particles (or salt or prodrug thereof) is used for all experiments.
- PBS buffer described above is used. Dissolve 704mg of sodium chloride (Fisher Scientific), 601.2 mg of sodium phosphate dibasic anhydrous (Fisher Scientific), 242.7 mg of sodium phosphate monobasic anhydrous (Fisher Scientific) with 140.4 g of sterile filtered DI water. The solution is cooled down in an ice chilled water bath and then 50g of poloxamer 407NF (SPECTRUM CHEMICALS) is sprinkled into the cold solution while mixing. The mixture is further mixed until the poloxamer is completely dissolved.
- poloxamer 407NF SPECTRUM CHEMICALS
- a series of formulations is prepared with the above stock solution.
- micronized/coated/liposomal particles (or salt or prodrug thereof) is used for all experiments.
- Tables 4 and 5 list samples prepared using the procedures described above. An appropriate amount of active agent is added to each sample to provide a final concentration of 2% active agent in the sample.
- HPLC analysis is performed using an Agilent 1200 equipped with a Luna C18(2) 3 ⁇ , lOOA, 250x4.6 mm column) using a 30-80 acetonitrile gradient (1-lOmin) of (water - acetonitrile mixture containing 0.05%TFA), for a total run of 15 minutes. Samples are diluted by taking 30 ⁇ ⁇ of sample and dissolving with 1.5mL of a 1 : 1 acetonitrile water mixture. Purity of the active agent in the autoclaved samples is recorded. The stability of formulations in TRIS and PBS buffers is compared.
- Viscosity measurements are performed using a Brookfield viscometer RVDV-II+P with a CPE-51 spindle rotated at 0.08 rpm (shear rate of 0.31 s "1 ), equipped with a water jacketed temperature control unit (temperature ramped from 15-34°C at 1.6 °C/min). Tgel is defined as the inflection point of the curve where the increase in viscosity occurs due to the sol-gel transition. Only formulations that show no change after autoclaving are analyzed.
- Formulations comprising gentamicin, ciprofloxacin and dexamethasone, are tested using the above procedure to determine the degradation products and viscosity of a formulation containing 2% active agent and 17% poloxamer 407NF after heat sterilization (autoclaving). Stability of formulations containing micronized active agent is compared to non-micronized active agent formulation counterparts.
- Example 22 In vitro comparison of relase profile.
- Dissolution is performed at 37°C in snapwells (6.5 mm diameter polycarbonate membrane with a pore size of 0.4 ⁇ ), 0.2 mL of a gel formulation described herein is placed into snapwell and left to harden, then 0.5 mL buffer is placed into reservoir and shaken using a Labline orbit shaker at 70 rpm. Samples are taken every hour (0.1 mL withdrawn and replace with warm buffer). Samples are analyzed for active agent concentration by UV at 245nm against an external calibration standard curve. Pluronic concentration is analyzed at 624 nm using the cobalt thiocyanate method. Relative rank- order of mean dissolution time (MDT) as a function of %P407 is determined.
- MDT mean dissolution time
- a linear relationship between the formulations mean dissolution time (MDT) and the P407 concentration indicates that the active agent is released due to the erosion of the polymer gel (poloxamer) and not via diffusion.
- a non-linear relationship indicates release of active agent via a combination of diffusion and/or polymer gel degradation.
- the MDT is inversely proportional to the release rate of an active agent from a composition described herein.
- the released active agent is optionally fitted to the Korsmeyer-Peppas equation:
- MDT mean dissolution time
- samples are analyzed using the method described by Li Xin-Yu paper [Acta Pharmaceutica Sinica 2008,43(2):208-203] and Rank-order of mean dissolution time (MDT) as a function of %P407 is determined.
- MDT mean dissolution time
- Formulations comprising gentamicin, ciprofloxacin and micronized dexamethasone, prepared according to the procedures described herein, are tested using the above procedure to determine the release profile of the active agents.
- compositions comprising varying concentrations of a gelling agent and micronized dexamethasone was prepared using procedures described above.
- the mean dissolution time (MDT) for each composition in Table 3 was determined using procedures described above.
- Method A Poloxamer 407 (BASF Corporation, lot WPEB612B) is dissolved in of 75/25 water/iso-propanol v/v solution. The solution is equilibrated to 27 °C. Sodium chloride is added with vigorous mixing and the solution is centrifuged to allow two clear, colorless phases to form. The lower phase is drained and the solution is again diluted to near its initial weight/volume by the addition of water/iso -propanol 75/25 v/v solution followed by equilibration to 27 °C and addition of sodium chloride. The solution is centrifuged to allow two clear, colorless phases to form.
- the lower phase is drained a second time and the solution returned to near its original weight by the addition of water/iso-propanol solution and sodium chloride as described earlier.
- the resulting solution is centrifuged, the lower phase is drained and discarded.
- the upper phase from the third extraction is dried then extracted with chloroform.
- the chloroform layer is then evaporated in vacuo. The residue is dried under vacuum.
- Method B Poloxamer 407 from BASF Corporation, Mount Olive, N.J., is dissolved in deionized water. The solution is maintained close to freezing, then ammonium sulfate is added. The solution is equilibrated at 2° C. and after two distinct phases are formed, the lower phase is discarded, and the upper phase is collected and weighed. Deionized water is added and the solution is equilibrated to 2°C. followed by addition of ammonium sulfate with stirring. After the salt is dissolved, the solution is maintained at approximately 2° C. until two phases formed. The upper phase is isolated and diluted with deionized water. The solution is chilled to about 2° C. and ammonium sulfate is added.
- the phases are allowed to separate as above.
- the upper phase is isolated and extracted with dichloromethane. Two phases are allowed to form overnight.
- the organic (lower) phase is isolated and dried over sodium sulfate.
- the dichloromethane phase is filtered through a PTFE filter (0.45 ⁇ pore size) to remove the undissolved salts.
- the dichloromethane is removed in vacuo and the residue is dried overnight in an oven.
- Example 25 Manufacturing and properties of a ciprofloxacin hydrogel formulations
- Dissolution was performed at 37°C in snapwells (6.5 mm diameter polycarbonate membrane with a pore size of 0.4 ⁇ ), 0.2 mL of gel was placed into snapwell and left to harden, 0.5 mL of 0.9% saline was placed into reservoir and shaken using a Labline orbit shaker at 70 rpm. Samples were taken every hour (All the saline withdrawn and replace with warm 0.9% saline with an osmolality of 290 mOsm). Samples were analyzed for Ciprofloxacin by HPLC.
- Tgel measurements were performed using a Brookfield viscometer RVDV-II+P with a CP-51 spindle rotated at 0.08 rpm (shear rate of 0.31 s "1 ) equipped with a temperature control unit (temperature ramped from 15-37°C at 1.6 °C/min).
- Viscosity was measured at 20°C using a Brookfield viscometer RVDV-II+P with a CP-40 spindle with a shear rate ramp from 7.5 to 375 s 1 . Data was fitted to the Casson model to calculate the plastic viscosity and yield stress of the drug product.
- Ciprofloxacin chromatographic purity is shown in the table below.
- the viscosity of ciprofloxacin suspensions in 16% poloxamer 407 were measured using a Brookfield viscometer RVDV-II+P with a CP -40 spindle with a ramp speed from 1- 50 rpm (shear rate from 7.5 to 375 s "1 ) or a CP-50 spindle with a ramp speed from 1-50 rpm (shear rate from 3.8 to 192 s "1 ), equipped with a temperature control unit (temperature set at 20°C).
- Ejection forces are directly proportional to the viscosity of the suspension as expressed by the Poiseuille's equation.
- Example 26 Treatment of sinusitis in an animal model
- the maxillary sinus ostium of white rabbits is obstructed with a pledget through an antrostomy created in the anterior face of the maxilla.
- the sinus is inoculated with
- Pseudomonas aeruginosa After 7 days, the antrostomy is reopened, the ostial obstruction is removed, and a single lumen catheter is placed. Normal saline is irrigated through the catheter for 7 days in one group of rabbits (placebo group), while a control group receives no irrigation. A third test group receives a single dose of a test sinonasal formulation. On day seven of the study, the rabbits are euthanized, analyzed under light microscopy, and bacterial counts of the nasal lavage are determined. Purulence, mucosal and underlying bony inflammation in both the control and the saline irrigation groups confirms presence of sinusitis.
- a reduction in bacterial counts in the nasal lavage, purulence and inflammation in the treatment group indicates an effective therapeutic outcome.
- Example 27 Determination of sustained release of an active agent in sinonasal structures
- sustained release of an active agent is determined in the nasal lavage or the sinus lavage using a suitable technique (e.g., UV spectrometry, HPLC, mass spectormety) for detection of active agent the lavage.
- a suitable technique e.g., UV spectrometry, HPLC, mass spectormety
- Epithelial scraping from sinonasal passages is used to determine tissue exposure of the active agent.
- Example 28 Clinical trial for evaluation of a sinonasal formulation in combination with surgery
- Example 29 Effect of sinonasal compositions in treatment of nasal polyposis
- the aim of this study is to determine whether administration of a sinonasal formulation of Example 9 reduces the size of nasal polyps, or reduces thickness of nasal polyps, and relieves symptoms in people with CRS.
- Subjects must meet the criteria for CRS, namely they must have (1) at least two major criteria (facial pain/pressure or headache, nasal congestion, anterior or posterior nasal drainage, hyposmia/anosmia) for at least 3 consecutive months; (2) an abnormal sinus CT scan in at least two sinus areas documented within 3 months of entry or endoscopic evidence of disease. Subjects must have bilateral polypoid disease
- Nasal polyps are defined as discreet polyps visible in the middle meatus area.
- Exclusion criteria Subjects who have received antibiotics within 3 weeks of the screening visit; Subjects with uncontrolled moderate to severe asthma (defined as FEV1 ⁇ 80% with asthma control Test ⁇ 19 for the week prior to entry), recent exacerbation, or use of systemic steroids burst within 6 weeks of study enrollment. Subjects who are receiving a maintenance dose of corticosteroid.
- Study design Patients are administered a single dose of a sinonasal composition of Example 19 via a catheter directly into the nasal polyp, or in the vicinity of the nasal polyp. Patients are monitored for one year.
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Abstract
La présente invention a pour objet des compositions et des méthodes pour le traitement de maladies ou d'états pathologiques nasosinusiens et/ou nasopharyngés au moyen de compositions et de formulations d'agent actif administrées localement à un individu souffrant d'une maladie ou d'un état pathologique nasosinusien ou nasopharyngé, par application directe de ces compositions et formulations sur ou par l'intermédiaire d'une perfusion dans la ou les structures nasosinusiennes ciblées.
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013009761A1 (fr) * | 2011-07-13 | 2013-01-17 | The Foundry, Llc | Procédés et appareil pour administrer un agent thérapeutique à des cibles de la muqueuse nasopharyngée |
US9220796B1 (en) | 2014-07-03 | 2015-12-29 | Otonomy, Inc. | Sterilization of ciprofloxacin composition |
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WO2022098525A1 (fr) * | 2020-11-05 | 2022-05-12 | Bravado Pharmaceuticals, LLC | Thérapie antivirale intranasale pour la protection des muqueuses contre des infections virales |
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Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2838111C (fr) | 2005-12-08 | 2016-01-19 | Insmed Incorporated | Compositions a base de lipide d'anti-infectieux pour traiter des infections pulmonaires et procedes d'utilisation de celles-ci |
AU2012211514B2 (en) * | 2006-10-24 | 2014-07-31 | Aradigm Corporation | Concentrated, inhalable ciprofloxacin formulation |
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US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
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WO2017105356A1 (fr) | 2015-12-18 | 2017-06-22 | Ak-Kim Kimya Sanayi Ve Ticaret Anonim Sirketi | Module de membrane à fibres creuses |
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US20180071281A1 (en) * | 2016-08-19 | 2018-03-15 | Gerbe Labs Inc. | Treating chronic rhinosinusitis |
EP3773505A4 (fr) | 2018-03-30 | 2021-12-22 | Insmed Incorporated | Procédés pour la fabrication continue de produits médicamenteux liposomaux |
CN110141559A (zh) * | 2019-06-18 | 2019-08-20 | 浦易(上海)生物技术有限公司 | 一种用于鼻粘膜的含药缓释微粒及其应用 |
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Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1164227B (it) * | 1983-05-13 | 1987-04-08 | Angeli Inst Spa | Composizione farmaceutica atta alla somministrazione nasale di sali quaternari d'ammonio ed attivita' anticolinergica |
GB9310412D0 (en) * | 1993-05-20 | 1993-07-07 | Danbiosyst Uk | Nasal nicotine system |
-
2010
- 2010-10-19 WO PCT/US2010/053217 patent/WO2011049960A2/fr active Application Filing
- 2010-10-21 WO PCT/US2010/053616 patent/WO2011050206A2/fr active Application Filing
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WO2011050206A3 (fr) | 2011-09-22 |
WO2011050206A2 (fr) | 2011-04-28 |
WO2011049960A9 (fr) | 2011-08-18 |
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