US20090149433A1 - Compositions for the treatment of inflammation of the gastrointestinal tract - Google Patents

Compositions for the treatment of inflammation of the gastrointestinal tract Download PDF

Info

Publication number
US20090149433A1
US20090149433A1 US12/269,765 US26976508A US2009149433A1 US 20090149433 A1 US20090149433 A1 US 20090149433A1 US 26976508 A US26976508 A US 26976508A US 2009149433 A1 US2009149433 A1 US 2009149433A1
Authority
US
United States
Prior art keywords
composition
esophagitis
corticosteroid
disease
inflammation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US12/269,765
Other languages
English (en)
Inventor
Elaine Phillips
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Meritage Pharma Inc
Original Assignee
Meritage Pharma Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40639386&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20090149433(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Meritage Pharma Inc filed Critical Meritage Pharma Inc
Priority to US12/269,765 priority Critical patent/US20090149433A1/en
Assigned to MERITAGE PHARMA, INC. reassignment MERITAGE PHARMA, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PHILLIPS, ELAINE
Publication of US20090149433A1 publication Critical patent/US20090149433A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/44—Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids

Definitions

  • Esophageal inflammation disorders are gaining increased recognition in both adults and children.
  • EE eosinophilic esophagitis
  • EE is an emerging, and fast-growing disorder characterized by high levels of eosinophils in the esophagus, as well as basal zone hyperplasia.
  • EE is thought to be provoked, in at least a subset of patients, by food allergies or airborne allergen exposure (1-5, 44).
  • EE diagnosis is often associated with other hypersensitivity disorders, including asthma, rhinitis, and other food and aeroallergen inhalant sensitivities (39-40).
  • Diagnosis is often made, e.g., in young children and depends on the finding of 15 to 20 or more to 24 or more eosinophils per high power field (eos/hpf) within esophageal mucosal biopsies (6-12).
  • EE gastroesophageal reflux disease
  • Symptoms of EE include, for example, abdominal pain, chest pain, choking, difficulty swallowing, failure to thrive, nausea, reflux not relieved by standard anti-flux therapy, skin rash or hives, vomiting, and weight loss. In one series, 15% of EE patients had concurrent developmental delay (45).
  • EE is becoming more frequently diagnosed throughout developing countries (7, 8, 13-16) many aspects of the disease remain unclear including its etiology, natural history and optimal therapy. Symptoms of EE often mimic those of GERD and include vomiting, dysphagia, pain and food impaction (8, 14, 17-20). However, treatment of EE and GERD differ and it is important to distinguish between them, particularly as untreated EE may be associated with esophageal narrowing in 10-30% of cases (14, 18, 20, 21). The overlap of GERD and EE symptoms is common; failure to respond to high PPI GERD treatment may be one diagnostic guideline for EE (42). The common occurrence regarding misdiagnosis of EE for GERD often results in delayed treatment for patients with EE. (42).
  • Certain embodiments of the present invention provide a method of treating, preventing or alleviating inflammation of the gastrointestinal tract comprising orally administering to an individual in need thereof a composition comprising a corticosteroid, a preservative, a chelating agent, an isotonic agent, a surfactant, and an excipient that increases the interaction of the composition with a mucosal layer.
  • the corticosteroid is, by way of non-limiting example, budesonide.
  • the corticosteroid is present in the composition in an amount of about 0.01 mg to about 1.0 mg of corticosteroid per gram of composition.
  • the corticosteroid is present in the composition in an amount of about 0.01 mg to about 1.0 mg of corticosteroid per mL of composition.
  • the present invention provides for methods of administering about 5 mL to about 50 ma of the corticosteroid containing composition to the individual.
  • the preservative is, by way of non-limiting example, potassium sorbate. In specific embodiments, the preservative is present in the composition in an amount of about 0.0002% to about 0.5% w/w of the composition.
  • the chelating agent is, by way of non-limiting example, disodium edetate. In specific embodiments, the chelating agent is present in the composition in an amount of about 0.0005% to about 0.1% w/w of the composition.
  • the isotonic agent is, by way of non-limiting example, dextrose.
  • the surfactant is, by way of non-limiting example, polysorbate 80.
  • the surfactant is present in the composition in an amount of about 0.0005% to about 2% w/w of the composition.
  • the excipient that increases the interaction of the composition with a mucosal layer is a viscosity modulator and/or modifier.
  • the viscosity modulator and/or modifier is selected from, by way of non-limiting example, microcrystalline cellulose, carboxymethyl cellulose sodium and a combination thereof.
  • the viscosity modulator and/or modifier is a combination of microcrystalline cellulose and carboxymethyl cellulose sodium.
  • the viscosity modulator and/or modifier is present in the composition in about 0.01% to about 3.0% w/w of the composition.
  • the viscosity modulator and/or modifier is Avicel® RC-591.
  • the composition has a first and a second excipient.
  • the second excipient is selected from an excipient that increases the interaction of the composition with a mucosal layer, a binder, a filler, a disintegrant, a diluent, a carrier, a vehicle and combinations thereof.
  • the second excipient that increases the interaction of the composition with a mucosal layer is a second viscosity modulator and/or modifier.
  • the second excipient is a vehicle (including a diluent) and is present in the composition in an amount of about 50% to about 99.5% w/w of the composition.
  • the vehicle is selected from, by way of non-limiting example, a liquid vehicle, a solid vehicle and combinations thereof.
  • the vehicle is a solid vehicle and is selected from, by way of non-limiting example, talc, bentonite, kaolin calcium carbonate, and combinations thereof.
  • the vehicle is a liquid vehicle and is selected from, by way of non-limiting example, water, ethanol, an organic solvent, an oil (e.g., corn oil) and combinations thereof.
  • the corticosteroid containing composition is formulated as a micronized suspension of the corticosteroid in an aqueous vehicle.
  • the corticosteroid containing composition has a target pH of about 4.5.
  • the target pH of the composition is attained by adding a pH adjusting agent to the composition.
  • the pH adjusting agent is, by way of non-limiting example, hydrochloric acid or sodium hydroxide.
  • the corticosteroid containing composition also contains, by way of non-limiting example, a sweetener, a flavoring agent or a combination thereof.
  • the corticosteroid containing composition contains budesonide as the corticosteroid, potassium sorbate as the preservative, disodium edetate as the chelating agent, dextrose as the isotonic agent, polysorbate 80 as the surfactant, a combination of microcrystalline cellulose and carboxymethyl cellulose sodium as the excipient that increases the interaction of the composition with a mucosal layer, and hydrochloric acid as the pH adjusting agent.
  • the corticosteroid containing composition contains about 0.01 mg to about 1.0 mg of budesonide per mL of composition, about 0.0002% to about 0.5% w/w of potassium sorbate, about 0.0005% to about 0.1% W/W of disodium edetate, about 0.0005% to about 2% w/w of polysorbate 80, and about 0.01% to about 3.0% w/w of a combination of microcrystalline cellulose and carboxymethyl cellulose sodium
  • the composition is further comprises an aqueous vehicle.
  • the corticosteroid containing composition is formulated as a micronized suspension of the budesonide in the aqueous vehicle.
  • the composition has a pH of about 4.5.
  • the composition comprises a second excipient that increases the interaction of the composition with a mucosal layer.
  • a pharmaceutical composition described comprises or a method described herein comprises administering (e.g., per day or per dose) to an individual about 0.1 mg to about 20 mg corticosteroid, about 1 to about 2 mg corticosteroid, about 2 to about 3 mg corticosteroid, or about 0.25- to about 2.5 mg, or about 0.25 to about 3 mg of corticosteroid.
  • the methods described herein of treating, preventing or alleviating inflammation of the gastrointestinal tract include treating, preventing or alleviating inflammation of the esophagus.
  • the individual has been diagnosed with (or has inflammation associated with), by way of non-limiting example, eosinophilic esophagitis, an inflammatory bowel disease involving the esophagus, Crohn's disease, esophageal inflammation secondary to caustic/irritant ingestion, persistent/recurrent esophageal strictures of any cause and including caustic/irritant ingestion, pill-induced esophagitis, systemic diseases, congenital diseases or post-surgery inflammation.
  • the individual has been diagnosed with (or has inflammation associated with), by way of non-limiting example, eosinophilic esophagitis.
  • the individual has been diagnosed with (or has inflammation associated with), by way of non-limiting example, gastroesophageal reflux disease (GERD), nonerosive reflux disease (NERD), or erosive esophagitis.
  • GFD gastroesophageal reflux disease
  • NERD nonerosive reflux disease
  • erosive esophagitis erosive esophagitis
  • the individual treated with the methods disclosed herein is a child or infant. In some embodiments, the child less than 19 years old, less than 16 years old, 12 years old, 8 years old, 6 years old, 4 years old, or 2 years old. In other embodiments, the individual is an adult.
  • FIG. 1 illustrates the percent amount of composition present in the esophagus as a function of time following oral administration (by measuring the amount of radiolabel present in the esophagus).
  • the present invention is directed to methods and pharmaceutical compositions for treating, preventing or alleviating the symptoms of and inflammation associated with inflammatory diseases involving the gastrointestinal tract, including the upper-gastrointestinal tract (e.g., inflammatory diseases involving pre-colonic gastrointestinal inflammation), esophagus, stomach and/or digestive tract.
  • inflammatory diseases involving the gastrointestinal tract including the upper-gastrointestinal tract (e.g., inflammatory diseases involving pre-colonic gastrointestinal inflammation), esophagus, stomach and/or digestive tract.
  • these methods comprise orally administering to said individual a corticosteroid in association with at least one excipient that increases the interaction of the composition with a surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus).
  • a surface of the gastrointestinal tract e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus.
  • the viscosity modulator and/or modifier provides an increased viscosity and the increased viscosity of the composition allows the composition to be in contact with the in esophagus for an extended period of time following administration.
  • An individual suitable for treatment with the compositions disclosed herein may, for example, have been diagnosed with a disease or condition including, but not limited to, eosinophilic esophagitis, inflammatory bowel diseases involving the esophagus, Crohn's disease, esophageal inflammation secondary to caustic/irritant ingestion, persistent/recurrent esophageal strictures of any cause and including caustic/irritant ingestion, pill-induced esophagitis, celiac disease, intermediate esophagitis, epithelial hyperplasia, basal cell hyperplasia, elongated papillae, dilated vessels in papillae, fungal esophagitis, viral esophagitis, bacterial esophagitis, corrosive esophagitis, radiation esophagitis, chemotherapy esophagitis, graft vs.
  • a disease or condition including, but not limited to, eosin
  • composition may also be used in treating other gastrointestinal disorders, including stomach and duodenal ulcers, hyperactive acidic discharge disorders, such as Zollinger-Ellison syndrome and laryngeal disorders.
  • the methods of the present invention are useful, for example, for treating, preventing and alleviating inflammation and/or symptoms and associated with eosinophilic esophagitis, inflammatory bowel diseases involving the esophagus, Crohn's disease, esophageal inflammation secondary to caustic/irritant ingestion, persistent/recurrent esophageal strictures of any cause and including caustic/irritant ingestion, pill-induced esophagitis, systemic diseases, congenital diseases, Epidermolysis bullosa, and post-surgery inflammation.
  • the present methods are also useful for treating, preventing or alleviating symptoms and/or inflammation associated with other diseases or conditions of the gastrointestinal tract, for example, the upper gastrointestinal tract, where it is beneficial to target a particular target site, rather than provide systemic therapy.
  • pharmaceutical compositions useful in the methods of the present application are useful in the methods of the present application.
  • inflammation and/or symptoms associated with a disorder or disease disclosed herein includes inflammation and/or symptoms associated with, caused by and/or resulting from the disorder or disease.
  • the term “individual” includes any animal. In some embodiments, the animal is a mammal. In certain embodiments, the mammal is a human. In specific embodiments, the human is an adult. In other embodiments, the human is a child. In yet other embodiments, the human is an infant.
  • the phrase “method of treating” or “method for treating” encompasses methods of preventing, reducing the incidences of, providing prophylactic treatment, treating and alleviating.
  • an effective amount and “a therapeutically effective amount” is an amount sufficient to elicit a change in the symptoms of or inflammation associated with gastrointestinal disorders, including but not limited to esophageal inflammation.
  • the term “or” includes “and” and “or”.
  • treating inflammatory diseases involving the esophagus includes treating symptoms of such diseases and treating inflammation associated with the diseases.
  • the corticosteroids used in the present invention include topical steroids including, for example, budesonide.
  • corticosteroids are selected from, by way of non-limiting example, aclometasone, amcinomide, beclometasone, betamethasone, budesonide, ciclesonide, clobetasol, clobetasone, clocortolone, cloprednol, cortivazol, deflazacort, deoxycorticosterone, desonide desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, fluclorolone, fludrocortisone, fludroxycortide, flumetasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin, fluocortolone, fluorometholone, fluperolone, flutica
  • compositions for treating, preventing or alleviating the symptoms of, and inflammation associated with, inflammatory diseases of the gastrointestinal tract including but not limited to the esophagus.
  • a corticosteroid e.g., budesonide
  • a corticosteroid that is administered in oral form, in a formulation with increased fluid viscosity, is delivered to the esophagus in an effective dose to reduce the inflammation of the esophagus.
  • an exemplary corticosteroid is budesonide.
  • Budesonide 16,17-(butylidenebis(oxy))-11,21-dihydroxy-, (11- ⁇ ,16- ⁇ )-pregna-1,4-diene-3,20-dione, is a corticosteroid sometimes used in inhaled form to treat pulmonary conditions.
  • the pharmaceutical composition described herein includes one or more excipients.
  • Excipients useful herein include, by way of nonlimiting example, binders, fillers, lubricants, isotonic agents, surfactants, antioxidants (e.g., chelating agents), preservatives, buffers, pH adjusting agents, solvents, flavoring agents, coloring agents, sweeteners, excipients that increase the interaction of the composition with a surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus) and combinations thereof.
  • a surface of the gastrointestinal tract e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus
  • Excipients that increase the interaction of the composition with the surface of the gastrointestinal tract include excipients that modulate and/or modify (e.g., enhance) the viscosity of the composition, excipients that impart a mucoadhesive characteristic to the composition, and excipients that enhance the absorption of the composition through a surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus).
  • surfactants are utilized in order to obtain an efficient dispersion of corticosteroid (e.g., budesonide) particles in the suspension.
  • Sweeteners include, by way of non-limiting example, sucrose, lactose, glucose, fructose, arabinose, xylose, ribose, mannoase, galactose, dextrose, sorbose, sorbitol, mannitol, maltose, cellobiose, xylitol and the like.
  • Flavoring agent include, by way of non-limiting example, peppermint, wintergreen, grape and cherry.
  • surfactants include, by way of non-limiting example, polysorbates (e.g., polysorbate 80), Tween®, poloxamers, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives and combinations thereof.
  • the surfactant is polysorbate 80.
  • an isotonic agent includes, by way of non-limiting example, dextrose, glycerin, mannitol, sodium chloride, potassium chloride and combinations thereof.
  • the isotonic agent is dextrose (e.g., dextrose anhydrous).
  • antioxidants or chelating agents include, by way of non-limiting example, edetate (e.g., disodium edetate) (EDTA).
  • edetate includes all compounds of Formula I wherein each R is independently selected from an H and a negative charge (e.g., as a salt or as a disassociated salt or acid).
  • edetate is selected from, by way of non-limiting example, disodium edetate, calcium edetate, ethylenediaminetetraacetic acid and the like.
  • Preservatives include, by way of non-limiting example, benzalkonium chloride, methylparaben, propylparaben, potassium sorbate and sodium benzoate.
  • the preservative is potassium sorbate.
  • the compositions comprise an excipient that increases the interaction of the composition with a surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus).
  • a surface of the gastrointestinal tract e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus.
  • the excipient or excipients chosen increase the interaction of the composition with the surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus) by at least 1.02 fold, by at least 1.05-fold, by at least 1.1 fold, by at least 1.2 fold, by at least 1.25-fold, by at least 1.5-fold, by at least 2-fold, by at least 3-fold, by at least 4-fold, by at least 5-fold, by at least 10 fold, or by at least 20 fold.
  • the surface of the gastrointestinal tract e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus
  • the increased interaction of the composition is an at least 1.02 fold, by at least 1.05-fold, by at least 1.1 fold, by at least 1.2 fold, by at least 1.25-fold, by at least 1.5-fold, by at least 2-fold, by at least 3-fold, by at least 4-fold or by at least 5-fold of interaction of the composition with the esophagus that occurs following passing of the bolus of the composition being swallowed.
  • these increases are measured and compared to the measure of an otherwise similar composition lacking the excipient or excipients that increase the interaction of the composition with the surface of the gastrointestinal tract.
  • increased interaction of the composition is measured as a function of the amount of composition present in the esophagus (e.g., after the bolus has passed through the esophagus).
  • the amount of composition present in the esophagus is measured in any suitable manner, e.g., by radiolabeling the composition and measuring the amount of the composition in the esophagus utilizing gamma scintigraphy.
  • An increase in the interaction of the composition with the surface of the gastrointestinal tract may be measured by measuring the retention time of the material along a length of a surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus), wherein the retention time is increased in the presence of the excipient as compared to its absence.
  • a portion composition is retained on the esophagus after oral administration (e.g., after initial swallowing) for at least 5 seconds, for at least 6 seconds at least 10 seconds, for at least 12 seconds, for at least 15 seconds, for at least 30 seconds, for at least 60 seconds, for at least 2 minutes, for at least 4 minutes, for at least 10 minutes, for at least 15 minutes, for at least 30 minutes, or the like.
  • the portion of the composition that is retained on or within the esophagus is at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 15%, at least 20%, at least 30%, at least 40%, at least 50%, or the like.
  • the composition is retained on the esophagus after oral administration for about 15 seconds to about 120 seconds, or for about 30 to about 90 seconds.
  • an increased interaction may be measured by the decrease in physiological manifestations or symptoms of the disease or ailment to be treated, including a decrease in total eosinophil counts in a particular gastrointestinal tissue sample.
  • a composition described herein to the esophagus e.g., following initial swallowing or drinking of the composition
  • at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% by weight of the corticosteroid or composition administered is present within the esophagus (e.g., as measured by gamma scintigraphy) after at least 5 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, 30 seconds, 40 seconds, 45 seconds, 50 seconds, or 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 or 60 minutes following application of the composition to the esophagus.
  • even small differences (e.g., increases) in adherence times (e.g., residence times) between formulations can result in therapeutically significant or clinically significant results or improvements.
  • the use of the excipients may act to decrease the quantity of active agents needed to elicit a response in the absence of the excipients.
  • the excipients may decrease the amount of corticosteroid used, for example, from about 1 to about 3 mg of budesonide in the absence of excipient to about 500 ⁇ g to about 2 mg of budesonide in the presence thereof.
  • the compositions provided herein may provide an additional advantage of decreasing the amount of active agent needed to treat subjects afflicted with inflammatory diseases involving the gastrointestinal tract, including the esophagus, stomach and/or digestive tract.
  • the corticosteroid is administered in combination with an excipient that enhances the viscosity of the composition.
  • the viscosity of the oral dosage form is at a level that is sufficient to deliver an effective amount of the composition to the site of gastrointestinal inflammation, e.g., the esophagus.
  • the effective amount of the composition delivered to the esophagus is an amount sufficient to coat the esophagus, and thereafter deliver the composition to the affected areas, including by way of example only, the lower esophagus, the esophageal-stomach juncture, the stomach and/or the duodenum.
  • the viscosity of the oral dosage form is such that when administered orally, it is not so thick as to cause difficulty in swallowing, cause gagging, or be unpalatable.
  • the viscosity of the compositions provided herein can determine the viscosity of the compositions provided herein, and may thus determine appropriate ranges.
  • the viscosity of the oral dosage form is a viscosity that is sufficient to provide exposure of the corticosteroid to the esophagus for a sufficient period of time such that the symptoms of and/or inflammation associated with inflammatory diseases involving the gastrointestinal tract, including the esophagus, are reduced following administration of the corticosteroid containing oral dosage form.
  • One method for determining sufficient viscosity may include monitoring changes in the interaction of the composition with a surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus), including but not limited to measuring changes in residence or retention time of the composition in the absence and presence of the excipient.
  • Another method for determining whether the composition is sufficiently viscous is by determining whether the inflammation of the esophagus is reduced after treatment with the composition.
  • Viscosity may be, for example, measured at room temperature, at about 20-25 degrees Celsius, or at about 37 degrees Celsius to mimic body temperature.
  • the viscosity of a liquid generally decreases as the temperature is raised.
  • the viscosity of the composition described herein is any viscosity suitable for delivery of the corticosteroid to the inflamed portion of the gastrointestinal tract.
  • the viscosity of the composition is at least about 2 centipoise (cP), at least about 25 cP, or at least about 50 cP. In some embodiments, the viscosity of the composition is at least about 100 cP.
  • the viscosity of the composition is from about 25 centipoise (cP) to about 800 cP, as measured with a Brookfield viscometer at 25 degrees Celsius, more preferably at about 50 cP to about 800, or about 300 eP to about 800 cP.
  • the viscosity of the composition may range from about 250 cP to about 600 cP or about 400 cP to about 600 cP.
  • the viscosity of the formulation is about 100 cP, about 200 cP, about 300 cP, about 400 cP or about 500 cP, as measured with a Brookfield viscometer at 25 degrees Celsius (e.g., equipped with an ultra low adapter).
  • Viscosity can also be determined by any method that will measure the resistance to shear offered by the substance or preparation. Many viscometers are available to those in the pharmaceutical field, and include those built by, for example, Brookfield.
  • the viscosity of the composition is measured at room temperature (about 25 degrees C.) with a shear rate of about 13.2 sec ⁇ 1 .
  • a composition having a viscosity under such conditions that is at least about 2 centipoise (cP), at least about 25 cP, at least about 30 cP, at least about 35 cP, about 35 cP, at least about 40 cP, about 40 cP, at least about 50 cP, at least about 200 cP, at least about 225 cP, at least about 250 cP, at least about 300 cP, or at least about 400 cP.
  • the viscosity of the composition under such conditions is about 50 cP to about 250,000 cP, about 50 cP to about 70,000 cP, about 50 cP to about 25,000 cP, about 50 cP to about 10,000 cP, about 50 cP to about 3,000 cP, about 50 cP to about 2,000 cP, about 250 cP to about 250,000 cP, about 250 cP to about 70,000 cP, about 250 cP to about 25,000 cP, about 250 cP to about 10,000 cP, about 250 cP to about 3,000 cP, or about 250 cP to about 2,000 cP.
  • the viscosity of the composition is from about 25 centipoise (cP) to about 800 cP, about 50 cP to about 800, or about 300 cP to about 800 cP (e.g., measured by a Brookfield viscometer).
  • the viscosity of the composition under such conditions may range from about 100 cP to about 200 cP, about 200 cP to about 300 cP, about 250 cP to about 600 cP or about 400 cP to about 600 cP.
  • the viscosity of the formulation measured under such conditions is about 30 cP, about 40 cP, about 100 cP, about 200 cP, about 300 cP, about 400 oP, about 500 oP, or about 250,000 cP.
  • the viscosity of the composition is measured at room temperature (about 25 degrees C.) with a shear rate of about 15 sec ⁇ 1 (e.g., with a gap between the spindle and the sample chamber wall of about 6 mm or greater).
  • a composition having a viscosity under such conditions that is at least about 150 centipoise (cP), at least about 160 cP, at least about 170 cP, at least about 180 cP, at least about 190 cP, or at least about 200 cP.
  • the viscosity of the composition under such conditions is about 150 cP to about 250,000 cP, 160 cP to about 250,000 cP, 170 cP to about 250,000 cP, 180 cP to about 250,000 cP, or 190 cP to about 250,000 cP.
  • Viscosity-enhancing excipients that may be used in pharmaceutical compositions described herein include, but are not limited to, acacia (gum arabic), agar, aluminum magnesium silicate, sodium alginate, sodium stearate, bladderwrack, bentonite, carbomer, carrageenan, Carbopol, xanthan, cellulose, microcrystalline cellulose (MCC), ceratonia, chondrus, dextrose, furcellaran, gelatin, Ghatti gum, guar gum, hectorite, lactose, sucrose, maltodextrin, mannitol, sorbitol, honey, maize starch, wheat starch, rice starch, potato starch, gelatin, sterculia gum, xanthum gum, polyethylene glycol (e.g.
  • PEG 2004500 gum tragacanth, ethyl cellulose, ethylhydroxyethyl cellulose, ethylmethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, poly(hydroxyethyl methacrylate), oxypolygelatin, pectin, polygeline, povidone, propylene carbonate, methyl vinyl ether/maleic anhydride copolymer (PVM/MA), poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), hydroxypropyl cellulose, hydroxypropylmethyl-cellulose (HPMC), sodium carboxymethyl-cellulose (CMC), silicon dioxide, polyvinylpyrrolidone (PVP: povidone), Splenda® (dextrose, maltodextrin and sucralose) or combinations thereof.
  • PVM/MA methyl vinyl ether/maleic anhydr
  • the viscosity-enhancing excipient is Splenda®.
  • the viscosity-enhancing excipient is a combination of MCC and CMC (e.g., Avicel® RC-591 (manufactured by FMC Corporation; colloid forming attrited mixture of microcrystalline cellulose and carboxymethylcellulose sodium, NF, BP; Avicel® RC-591 product brochure, RC-591 (5/99) is hereby incorporated by reference in its entirety)).
  • a composition described herein comprises a first viscosity enhancing agent (e.g., Avicel®3 RC-591) and a second viscosity enhancing agent (e.g., Splenda®).
  • Mucoadhesive agents including, but not limited to, at least one soluble polyvinylpyrrolidone polymer (PVP); a water-swellable, but water-insoluble, fibrous, cross-linked carboxy-functional polymer; a crosslinked poly(acrylic acid) (e.g. Carbopol 947P); a carbomer homopolymer; a carbomer copolymer; a hydrophilic polysaccharide gum, maltodextrin, a cross-linked alignate gum gel, a water-dispersible polycarboxylated vinyl polymer, at least two particulate components selected from the group consisting of titanium dioxide, silicon dioxide, and clay, or a mixture thereof.
  • PVP polyvinylpyrrolidone polymer
  • a water-swellable, but water-insoluble, fibrous, cross-linked carboxy-functional polymer e.g. Carbopol 947P
  • a carbomer homopolymer e.g. Carbo
  • the mucoadhesive agent may be used in combination with a viscosity increasing excipient, or may be used alone to increase the interaction of the composition with the esophagus.
  • the mucoadhesive agent is maltodextrin.
  • the mucoadhesive character imparted to the composition should be at a level that is sufficient to deliver an effective amount of the composition to, for example, the esophagus in an amount that may coat the esophagus, and thereafter deliver the composition to the affected areas, including by way of example only, the lower esophagus, the esophageal-stomach juncture, the stomach and/or the duodenum.
  • the mucoadhesiveness should be at a level that may be given orally, i.e. allows a patient to swallow, limits a gagging reaction, and is palatable.
  • a mucoadhesive agent is an agent that adheres to a gastrointestinal surface (e.g., either or both of a gastrointestinal epithelia or mucosa).
  • Mucoadhesive agents have been described, for example, in U.S. Pat. Nos. 6,638,521, 6,562,363, 6,509,028, 6,348,502, 6,319,513, 6,306,789, 5,814,330, and 4,900,552, each of which is hereby incorporated by reference in its entirety.
  • the mucoadhesive agent is maltodextrin.
  • Maltodextrin is a carbohydrate produced by the hydrolysis of starch that may be derived from corn, potato, wheat or other plant products. Maltodextrin may be used either alone or in combination with other mucoadhesive agents to impart mucoadhesive characteristics on the compositions disclosed herein. In one embodiment, a combination of maltodextrin and a carbopol polymer are used to increase the mucoadhesive characteristics of the compositions disclosed herein.
  • any composition or formulation described herein comprises greater than about 7% w/w, greater than about 8% w/w, greater than about 9% w/w, greater than about 10% w/w, greater than about 11% w/w, greater than about 12% w/w, greater than about 13% w/w, greater than about 14% w/w, greater than about 15% w/w, greater than about 16% w/w, greater than about 17% w/w, greater than about 18% W/W, greater than about 19% w/w, greater than about 20% w/w, greater than about 21% wows greater than about 22% w/w, greater than about 23% w/w, greater than about 24% w/w, greater than about 25% w/w, greater than about 26% w/w, greater than about 27% w/w, greater than about 28% w/w, greater than about 29% w/w or greater than about 30% w/w of maltodextrin.
  • the maltodextrin is substantially dissolved in a liquid vehicle of the composition or formulation.
  • the maltodextrin has a dextrose equivalents (DE) of greater than 4, greater than 5, greater than 10, greater than 11, greater than 12, greater than 13, greater than 14, greater than 15, about 15, about 4 to about 10, about 4 to about 9, about 4 to about 8, about 11 to about 20, about 12 to about 19, about 13 to about 18, or about 14 to about 16.
  • the first maltodextrin has a DE of about 4 to about 10, about 4 to about 9, or about 4 to about 8 and the second maltodextrin has a DE of about 10 to about 20, about 12 to about 19, or about 13 to about 18.
  • at least one maltodextrin utilized in a composition described herein has a molecular weight high enough to increase the solubility of a corticosteroid, or to increase the suspendability of a corticosteroid particle.
  • a mucoadhesive agent can be, for example, at least two particulate components selected from titanium dioxide, silicon dioxide, and clay, wherein the composition is not further diluted with any liquid prior to administration and the level of silicon dioxide, if present, is from about 3% to about 15%, by weight of the composition.
  • Silicon dioxide if present, may be selected from the group consisting of fumed silicon dioxide, precipitated silicon dioxide, coacervated silicon dioxide, gel silicon dioxide, and mixtures thereof.
  • Clay if present may be kaolin minerals, serpentine minerals, smectites, illite or a mixture thereof. For example, clay can be laponite, bentonite, hectorite, saponite, montmorillonites or a mixture thereof.
  • compositions comprising a viscosity enhancing agent and a mucoadhesive agent.
  • the composition comprises about 0.005% (w/w) to about 3% (w/w) of a viscosity enhancing excipient (e.g., a CMC/MCC combination having a ratio as described herein), and about 1% (w/w) to about 30% (wsw) of a mucoadhesive agent (e.g., maltodextrin).
  • absorption enhancing examples include, but are not limited to, acylcarnitines, surfactants, sodium lauryl sulfate, saponins, bile salts or bile acids including but not limited to cholanic acid, chilic acid, deoxycholic acid, glycocholic acid, tautocholic acid, chenodeoxycholic acid, lithocholic acid, ursocholic acid, ursodeoxycholic acid, isourosde oxycholic acid, lagodeoxycholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, dehydrocholic acid, hyocholic acid, hyodeoxycholic acid, or combinations thereof, dihydrofuisidates, fatty acid derivatives, chitosan, carbopol, cellulosic agents, sterols, including but not limited to alcohols structurally related to steroids, including but not limited to cholestanol, coprostanol, cholesterol, epicholesterol, er
  • Absorption enhancing agents may act by increasing absorption of the active agent, including corticosteroids and acid inhibitors, through a surface of the gastrointestinal tract (e.g., the mucosa and/or epithelium of the gastrointestinal tract or of a specific site of the gastrointestinal tract, such as the esophagus). Examples of absorption enhancing agents are disclosed in WO 2005/113008, which is hereby incorporated by reference in its entirety.
  • compositions contemplated herein may also include a combination of excipients that are viscosity enhancing agents, mucoadhesive agents and/or absorption enhancing agents. Moreover, an excipient may exhibit multiple characteristics, i.e. may be both a viscosity enhancing agent and a mucoadhesive agent. The composition may also include excipients that do not impart characteristics of viscosity enhancing, mucoadhesive agents or absorption enhancing activity.
  • the pharmaceutical compositions provided herein is used to treat, prevent or alleviate inflammatory diseases involving the gastrointestinal tract, including the esophagus, stomach and/or digestive tract.
  • the pharmaceutical composition is in liquid form.
  • Liquid forms include, by way of non-limiting example, solutions, suspensions, syrups, slurries, dispersions, colloids and the like.
  • the liquid is a suspension.
  • the methods and compositions of the present invention are used by individuals of any age.
  • “individual” is meant any animal, for example, a mammal, or, for example, a human, including, for example, patients in need of treatment.
  • the individual is a human adult.
  • the individual is a human child or infant.
  • the human child or infant is less than 16 years old, less than 12 years old, less than 8 years old, less than 6 years old, less than 4 years old or less than 2 years old.
  • compositions of the present invention will typically be used in therapy for human patients, in certain embodiments, they are used in veterinary medicine to treat similar or identical diseases.
  • the compositions are used, for example, to treat mammals, including, but not limited to, primates and domesticated mammals.
  • the compositions are used, for example, to treat herbivores.
  • the compositions of the present invention include geometric and optical isomers.
  • compositions suitable for use in the present invention include compositions wherein the active ingredient or ingredients are contained in an effective amount to achieve its intended purpose.
  • determination of the effective amounts is well within the capability of those skilled in the art. It is expected that a skilled pharmacologist may adjust the amount of drug in a pharmaceutical composition or administered to a patient based upon standard techniques well known in the art.
  • the exact dosage will depend upon the route of administration, the form in which the composition is administered, the subject to be treated, the age, body weight/height of the subject to be treated, and the preference and experience of the attending physician.
  • the optimal concentration of the corticosteroid in the composition depends upon the specific corticosteroid used, the characteristics of the patient, and the nature of the inflammation for which the treatment is sought. In various embodiments, these factors are determined by those of skill in the medical and pharmaceutical arts in view of the present disclosure.
  • a therapeutically effective dose refers to the amount of the corticosteroid that results in a degree of amelioration of symptoms and inflammation relative to the status of such symptoms prior to treatment.
  • the dosage forms containing effective amounts are within the scope of the instant invention.
  • the amount of corticosteroid (e.g., budesonide) used in a method or in a composition described herein is from about 2.5 to 400 ⁇ g/kg of body weight per day, or for example, in the range of 5 to 300 ⁇ g/kg per day, or for example in the range of 5 to 200 ⁇ g/kg per day, or for example in the range of 5 to 100 ⁇ g/kg per day, or for example in the range of 10 to 100 ⁇ g/kg per day, or for example in the range of 10-50 ⁇ g/kg per day, or for example in the range of 10-100 ⁇ g/kg/day, or for example in the range of 5-50 ⁇ g/kg/day, or in an illustrative embodiment in the range of 10-60 ⁇ g/kg/day.
  • corticosteroid e.g., budesonide
  • the amount of corticosteroid (e.g., budesonide) used in a method or in a combination disclosed herein includes, by way of non-limiting example, 250 ⁇ g to 3 mg, or 500 ⁇ g to 3 mg, or 500 ⁇ g to 2 mg, or 1 mg to 3 mg.
  • the dosage is provided in a sufficient volume to allow the composition to reach the esophagus in an effective amount.
  • a dosage or amount (including a divided dose) of corticosteroid is provided in a composition of sufficient volume to allow any of the compositions disclosed herein to reach the targeted and/or inflamed portion of the gastrointestinal tract, including, e.g., the esophagus, in an effective amount.
  • the effective amount of the composition delivered to the esophagus is an amount sufficient to coat or at least partially coat the esophagus, and deliver the composition to the affected areas, including by way of example only, the lower esophagus, the esophageal-stomach juncture, the stomach and/or the duodenum.
  • about 0.25 mg to about 6 mg, about 0.375 mg, about 0.5 mg, about 0.75 mg, about 1 mg, about 1.25 mg, about 1.5 mg, or about 2 mg of corticosteroid (e.g., budesonide) is formulated into a single or unit dose of a pharmaceutical composition described herein, the single or unit dose having a total volume of about 1-20 mL, or for example about 10-20 mL, or for example about 10 mL, or for example, about 15 mL, or for example, about 20 mL, or for example about 1-15 mL, or for example about 1-10 mL, or for example about 2-8 mL, or for example about 3-7 mL, or for example, about 4-6 mL, or for example, about 5 mL, or for example about 6-14 mL, or for example about 8-12 mL, or for example, about 9-11 mL, or for example, about 10 ml.
  • corticosteroid e.g., budeson
  • an appropriate palatable dosage is in a volume sufficient to coat or at least partially coat the esophagus, and in an illustrative embodiment, the volume is sufficient to coat or at least partially coat the esophagus and deliver the corticosteroid to the affected areas, including by way of example only, the lower esophagus, the esophageal-stomach juncture, the stomach, the duodenum and/or within 3 cm of the Z-line.
  • the composition may be delivered, for example, four times a day, three times a day, twice a day, once a day, every other day, three times a week, twice a week, or once a week.
  • the dosage may, for example, be divided into multiple doses throughout the day, or be provided, for example, in four, three, two, or one dose a day.
  • administration more frequent administration e.g., b.i.d. versus once a day
  • the dose is provided once a day.
  • a dose or composition described herein is administered with food. In some embodiments, a dose or composition described herein is administered without food. In certain embodiments, a dose or composition described herein is administered in a fed or fasted state. In some embodiments, a dose or composition described herein is administered in the morning, in the afternoon, in the evening, at night, or a combination thereof. In some embodiments, the dose is administered at night. In another aspect, the dose is administered about 30 minutes prior to bed, with no food or water given after administration of the compositions herein.
  • the dose is administered prior to bedtime, wherein after administration of the composition, the patient or individual is in a substantially supine position for at least 30 minutes, at least 1 hour, at least 2 hours, at least 4 hours or at least 8 hours.
  • administering a single unit dose from a multi dose container comprises (1) shaking a multidose container, the multidose container comprising at least one unit dose of a pharmaceutical composition described herein; (2) pouring a single unit dose from the multidose container into an administration device (e.g., a device suitable for administering to a human individual, such as a spoon, cup or syringe); and (3) administering the single unit dose to the individual in need thereof.
  • an administration device e.g., a device suitable for administering to a human individual, such as a spoon, cup or syringe
  • shaking of the multidose container occurs until the fluid therein has a viscosity suitable for pouring (e.g., easy pouring).
  • the process further comprises waiting after pouring the single unit dose and prior to administering the single unit dose to the individual in need thereof.
  • the wait time is a time sufficient to allow the viscosity of composition to achieve a desired level, e.g., a viscosity to improve the coating capabilities of the composition.
  • the wait time is, e.g., about 3 seconds, or more; about 5 seconds, or more; about 10 seconds, or more; about 15 seconds, or more; about 20 seconds, or more; about 25 seconds, or more; about 30 seconds, or more; about 40 seconds, or more; about 45 seconds, or more; about 50 seconds, or more; or about 60 seconds, or more.
  • the composition is administered immediately following pouring the composition into the administration device.
  • the process comprises shaking the multidose container well.
  • a multiple unit container comprising about 2 to about 180, about 10 to about 60, about 14, or about 30 unit doses of any pharmaceutical composition described herein.
  • each dose comprises about 1 mL to about 25 mL, about 1 mL to about 20 mL, about 7 mL to about 25 mL, about 10 to about 20 mL, about 15 mL, about 20 mL, about 3 to about 7 mL, about 5 mL, about 8 mL to about 12 mL, or about 10 mL.
  • each dose comprises about 0.1 to about 20 mg, about 0.1 to about 10 mg, about 0.1 to about 7.5 mg, about 0.1 to about 5 mg, about 0.3 to about 4 mg, about 0.25 to about 2.5 mg, about 0.3 mg to about 2 mg, about 0.5 mg to about 1 mg, about 0.7 mg to about 1.5 mg, about 0.375 mg, about 0.75 mg, about 1 mg, about 1.25 mg, about 1.5 mg or about 2 mg of corticosteroid.
  • a multiple unit container comprising about 10 mL to about 1500 mL, about 50 mL to about 600 mL, about 150 mL, about 300 mL, about 600 mL, or about 1,200 mL of any pharmaceutical composition described herein.
  • the multidose container comprises about 330 mL or about 55 mL of a composition described herein.
  • a kit provided herein comprises any multidose container as described herein, a pharmaceutical composition as described herein (e.g., in a volume described), and a delivery or metered device (e.g., a syringe, a cup, a spoon, or the like).
  • the delivery or metered device is incorporated into the container (e.g., a nebulizer, an aerosolizer, a pump, or the like).
  • the delivery or metered device is separate from the container.
  • the pharmaceutical composition contained within any of the multiple unit containers described herein is physically and chemically stable.
  • the corticosteroid is budesonide and the composition comprises about 0.01 mg to about 1.0 mg of budesonide/g of composition. In some embodiments, the composition comprises about 0.1 mg to about 1.0 mg of budesonide/g of composition. In certain embodiments, the composition comprises about 0.3 mg to about 0.6 mg of budesonide/g of composition. In specific embodiments, the composition comprises about 0.4 mg or 0.44 mg of budesonide/g of composition. In certain specific embodiments, the composition comprises about 3.8 mg/8.6 g of composition. In some embodiments, the composition comprises about 0.01 mg to about 1.0 mg of budesonide/mL of composition (about 0.001 to about 0.1% w/w).
  • the composition comprises about 0.1 mg to about 1.0 mg of budesonide/mL of composition (about 0.01 to about 0.1% w/w). In certain embodiments, the composition comprises about 0.3 mg to about 0.8 mg of budesonide/mL of composition (about 0.03 to about 0.08% w/w). In specific embodiments, the composition comprises about 0.6 to about 0.7 mg of budesonide/mL of composition (about 0.06 to about 0.07% w/w). In more specific embodiments, the composition comprises about 0.63 mg of budesonide/mL of composition (about 0.063% w/w).
  • the corticosteroid containing composition comprises budesonide, a viscosity enhancing agent, a preservative, an antioxidant (including, e.g., a chelating agent), an isotonic agent, a surfactant, an aqueous vehicle, an optional pH adjusting agent and an optional sweetener.
  • the composition is a liquid.
  • the liquid composition is a suspension.
  • a viscosity enhancing agent is present in about 0.005% to about 3.0% w/w of the composition. In certain embodiments, a viscosity enhancing agent is present in about 0.1% to about 3.0% w/w of the composition. In specific embodiments, a viscosity enhancing agent is a combination of microcrystalline cellulose and carboxymethyl cellulose (e.g., carboxymethyl cellulose sodium), such as Avicel RC-591. In more specific embodiments, the combination of MCC and CMC are present in an amount of about 0.05% to about 2.5% w/w (or about 0.5% to about 2.5% w/w) of the composition.
  • a viscosity enhancing agent is selected from, by way of non-limiting example, xanthan gum at about 0.03% to about 3% w/w (or about 0.3% to about 3% w/w), carbomer at about 0.01% to about 2% w/w (or about 0.1% to about 2% w/w), guar gum at about 0.03% to about 2% w/w (or about 0.3% to about 2% w/w), or RPMC at about 0.05% to about 3.0% w/w (or about 0.5% to about 3.0% w/w) of the composition.
  • one or more additional viscosity enhancing agents are added so as to provide a viscosity as described herein.
  • the amount of an aforementioned viscosity enhancing agent present in the composition is increased so as to provide a viscosity as described herein.
  • the CMC/MCC combination e.g., Avicel® RC-591
  • the CMC/MCC mixed weight ratio is between about 1/99 and about 99/1, about 20/80 and about 5/95, or about 15/85 and about 10/90.
  • the CMC is NaCMC and the CMC/MCC mixed weight ratio is about 11/89.
  • surfactants include, by way of non-limiting example, polysorbates (e.g., polysorbate 80), poloxamers, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives and combinations thereof.
  • surfactants are present in an amount of about 0.0005% to about 2% w/w (or about 0.005% to about 2% w/w) of the composition.
  • the surfactant is polysorbate 80.
  • polysorbates are present in an amount of about 0.0005% to about 2% w/w (or about 0.005% to about 2% w/w) of the composition.
  • poloxamers are present in an amount of about 0.001% to about 2% w/w (or about 0.01% to about 2% w/w) of the composition
  • polyoxyethylene alkyl ethers are present in an amount of about 0.001% to about 1% w/w (or about 0.01% to about 1% w/w) of the composition
  • polyoxyethylene castor oil derivatives are present in an amount of about 0.001% to about 1% w/w (or 0.01% to about 1% w/w) of the composition.
  • an isotonic agent includes, by way of non-limiting example, dextrose, glycerin, mannitol, sodium chloride, potassium chloride and combinations thereof.
  • the isotonic agent is dextrose (e.g., dextrose anhydrous).
  • the isotonic agent is included in any suitable amount, such as, by way of non-limiting example, between about 0.5 mg and about 0.5 g per gram of composition.
  • the isotonic agent is included in an amount of about 10 mg and about 100 mg or about 40 mg to about 60 mg per gram of composition.
  • chelating agents include, by way of non-limiting example, disodium edetate (EDTA).
  • EDTA disodium edetate
  • the chelating agent is present in an amount of about 0.0005% to about 0.1% w/w (or about 0.005% to about 0.1% w/w) of the composition.
  • Preservatives include, by way of non-limiting example, benzalkonium chloride, methylparaben, propylparaben, potassium sorbate and sodium benzoate.
  • the preservative is potassium sorbate.
  • the preservative is present in an amount of about 0.0002% to about 0.5% w/w (or about 0.002% to about 0.5% w/w) of the composition.
  • benzalkonium chloride is present in an amount of about 0.0002% to about 0.02% w/w (or about 0.002% to about 0.02% w/w) of the composition
  • methylparaben is present in an amount of about 0.005% to about 0.25% w/w (or about 0.05% to about 0.25% w/w) of the composition
  • propylparaben is present in an amount of about 0.001% to about 0.2% w/w (or about 0.01% to about 0.2% w/w) of the composition
  • potassium sorbate is present in an amount of about 0.005% to about 2.0% w/w (or about 0.05% to about 2.0% w/w) of the composition
  • sodium benzoate is present in an amount of about 0.01% to about 0.5% w/w (or about 0.1% to about 0.5% w/w) of the composition.
  • Sweeteners include, by way of non-limiting example, sucralose, sucrose, lactose, glucose, fructose, arabinose, xylose, ribose, mannose, galactose, dextrose, sorbose, sorbitol, mannitol, maltose, cellobiose, xylitol, honey and the like.
  • the sweetener is utilized in an amount sufficient to at least partially mask the taste of the composition and/or the corticosteroid (e.g., budesonide).
  • the corticosteroid containing composition comprises micronized budesonide, microcrystalline cellulose, carboxymethyl cellulose sodium, dextrose anhydrous, polysorbate 80, disodium edetate, potassium sorbate, water, optionally hydrochloric acid and optionally one or more additional excipient.
  • the composition has a pH of about 4.5.
  • at least one of the optional excipients is a sweetener, a flavoring agent, or a combination thereof.
  • the composition administered comprises a micronized suspension of budesonide in an aqueous medium.
  • microcrystalline cellulose and carboxymethyl cellulose sodium, dextrose anhydrous, polysorbate 80, disodium edetate, potassium sorbate, and purified water are contained in the aqueous medium.
  • hydrochloric acid is added to adjust the pH to a target of about 4.5.
  • the compositions provided herein are prepared utilizing any suitable source of active agents.
  • corticosteroid (e.g., budesonide) used in the compositions described herein are neat corticosteroid (e.g., budesonide).
  • the neat corticosteroid (e.g., budesonide) is neat, bulk corticosteroid.
  • the neat corticosteroid e.g., budesonide
  • the neat corticosteroid is powder corticosteroid (e.g., budesonide).
  • the neat corticosteroid e.g., budesonide
  • the neat corticosteroid is micronized corticosteroid (e.g., budesonide).
  • the composition comprises Rhinocort Aqua® (manufactured by AstraZeneca; Rhinocort Aqua® Nasal Spray; 32 mcg of budesonide per spray and 120 metered sprays after initial priming; package insert 30516-00, Rev. 01/05, is hereby incorporated by reference in its entirety), an optional diluent, and an optional sweetener.
  • the diluent is any carrier suitable for oral administration, including, by way of non-limiting example, water, ethanol, and combinations thereof. In a specific embodiment, the diluent is water.
  • the composition comprises Rhinocort Aqua®, an additional viscosity enhancing agent (e.g., Splenda), an optional diluent, and an optional sweetener and/or flavoring agent.
  • a composition useful herein includes a composition comprising a composition described in U.S. Pat. No. 6,291,445, U.S. Pat. No. 6,686,346, or U.S. Pat. No. 6,986,904, an optional additional viscosity enhancing agent or “thickener”, an optional diluent, and an optional sweetener and/or flavoring agent.
  • the composition comprises Rhinocort Aqua® and a diluent wherein the Rhinocort Aqua® and diluent are present in a ratio between about 1:0.5 and about 1:100.
  • the diluted Rhinocort Aqua® composition further comprises an excipient that increases the interaction of the composition with a surface of the gastrointestinal tract (e.g., a viscosity enhancing agent).
  • initial treatment continues, for example, for about 3 days to 2 weeks for an acute condition, or about 4 weeks to about 16 weeks for a chronic condition, or about 8 weeks to about 12 weeks for a chronic condition.
  • longer therapy is needed, such as, for example, therapy similar to chronic therapy for persistent asthma.
  • patients are, for example, be treated for up to 6 months, or up to one year.
  • maintenance treatments last up to or longer than one year.
  • patients are treated on a maintenance basis or on an as needed basis during a problematic episode, depending on the severity of the condition.
  • patients are treated on a rotating treatment basis, where treatment is provided for a period of time and then the patient is taken off of the drug for a period before treatment resumes again.
  • the patient may be given no treatment, treatment with another medication, dietary therapy, or treatment with a reduced dosage.
  • patients are given treatment with a higher dose of the composition until a desired reduced disease state is achieved, and then continued on a lower dose of the composition.
  • a patient combines treatment with a composition described herein with a treatment with another medication, and/or dietary therapy.
  • patients are given treatment with a higher dose of the composition until a desired reduced disease state is achieved, and then continued on a lower dose of the composition.
  • compositions of the present invention include pharmaceutically acceptable salts.
  • Pharmaceutically acceptable salts are generally well known to those of ordinary still in the art and include, by way of non-limiting example, acetate, atosylate, benzenesulfonate, besylate, benzoate, bicarbonate, bitartrate, bromide, calcium edetate, carnsylate, carbonate, citrate, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutarnate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, mucate, napsylate, nitrate, pamoate (embonate), pantothen
  • salts may be found in, for example, Remington: The Science and Practice of Pharmacy (20th ed.) Lippincott, Williams & Wilkins (2000).
  • pharmaceutically acceptable salts include, for example, acetate, benzoate, bromide, carbonate, citrate, gluconate, hydrobromide, hydrochloride, maleate, mesylate, napsylate, pamoate (embonate), phosphate, salicylate, succinate, sulfate, or tartrate.
  • such salts are used for any of the corticosteroids described herein.
  • the compositions is formulated into liquid or solid dosage forms and administered systemically or locally.
  • the agents are delivered, for example, in a timed- or sustained-low release form as is known to those skilled in the art. Techniques for formulation and administration may be found in Remington: The Science and Practice of Pharmacy (20th ed.) Lippincott, Williams & Wilkins (2000).
  • the composition is formulated as a liquid dosage form.
  • the liquid dosage form is a suspension of micronized corticosteroid (e.g., budesonide) particles.
  • compositions that contain suitable pharmaceutically acceptable excipients and auxiliaries.
  • pharmaceutically acceptable excipients and/or auxiliaries are used to formulate the corticosteroids herein disclosed for the practice of the invention into dosages suitable for systemic administration is within the scope of the invention.
  • the corticosteroid is formulated readily using pharmaceutically acceptable excipients and/or auxiliaries well known in the art into dosages suitable for oral administration.
  • compositions of the invention enable the compositions of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated.
  • pharmaceutical preparations for oral use are obtained by combining an aqueous formulation of a corticosteroid (e.g., budesonide) with solid excipients, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores.
  • solid oral dosage forms e.g., tablets, dragee cores, capsules, push-fit capsules, soft capsules, lozenges, etc.
  • solid oral dosage forms are formulated such that the dosage forms substantially dissolve or disintegrate in the mouth and/or esophagus.
  • solid oral dosage forms are formulated such that the dosage forms substantially dissolve or disintegrate prior to reaching the stomach.
  • an oral dosage form has substantially dissolved or disintegrated if at least 50%, by weight, of the dosage form has dissolved or disintegrated.
  • substantial dissolution or disintegration includes at least 60%, 70%, 80%, 90% or 95% by weight.
  • Suitable excipients include, by way of non-limiting example, fillers such as sugars or starches, including dextrose, lactose, maltodextrin, sucrose, sucralose, mannitol, or sorbitol; cellulose preparations, for example, maize starch, wheat starch, rice starch, potato starch, or a combination thereof.
  • the aqueous formulation comprises budesonide, a viscosity enhancing agent, a preservative, a chelating agent, an isotonic agent, a surfactant, an optional pH adjusting agent and an optional sweetener.
  • the aqueous formulation comprises budesonide, microcrystalline cellulose and carboxymethyl cellulose sodium, dextrose anhydrous, polysorbate 80, disodium edetate, potassium sorbate, and hydrochloric acid to adjust the pH to a target of about 4.5 (e.g., Rhinocort Aqua®).
  • the aqueous solvent is removed (e.g., by evaporation).
  • Disintegrating agents are optionally added, such as the cross-linked polyvinylpyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.
  • the pharmaceutical compositions used herein include excipients suitable for rendering the dissolving tablet palatable, such as sweeteners or flavoring agents.
  • the pharmaceutical compositions described herein are in liquid form.
  • Appropriate excipients for use in liquid form pharmaceutical compositions include, for example, those that increase the liquid viscosity of the liquid composition.
  • Optional excipients also include, by way of non-limiting example, those that render the liquid composition palatable.
  • Optional excipients include, by way of non-limiting example, sugars, including dextrose, lactose, sucrose, sucralose, maltodextrin, mannitol, or sorbitol; honey or combinations thereof.
  • Dragee cores are provided with suitable coatings.
  • suitable coatings In some embodiments, concentrated sugar solutions are used for this purpose, which optionally contain gum arabic, talc, polyvinylpyrrolidone, carbopol gel, polyethylene glycol (PEG), and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures.
  • Dye-stuffs or pigments are optionally added to the tablets or dragee coatings for identification or to characterize different combinations of active corticosteroid doses.
  • pharmaceutical preparations that are used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin, and a plasticizer, such as glycerol or sorbitol.
  • the push-fit capsules contain the active ingredient or ingredients in admixture with a filler, binder, lubricant, stabilizer or a combination thereof.
  • Fillers include, by way of non-limiting example, lactose.
  • Binders include, by way of non-limiting example, starches.
  • Lubricants include, by way of non-limiting example, talc and magnesium stearate.
  • the corticosteroids may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols (PEGs).
  • stabilizers are optionally added.
  • the present invention provides for a corticosteroid that has a low bioavailability. Due to the low bioavailability, the corticosteroid is used in certain embodiments of the invention, the corticosteroid remains in the gastrointestinal tract, for example, in the esophagus. In some embodiments, the low bioavailability results in decreased systemic side effects and complications, allowing patients with chronic conditions to receive treatment for longer periods of time.
  • diseases or conditions that are treated, prevented, or exhibit an alleviation of symptoms by administering a composition described herein include any disease or condition that involves inflammation of the gastrointestinal tract, including the esophagus, stomach and/or digestive tract. This includes, by way of non-limiting example, any chronic inflammatory or malignant state that involves the gastrointestinal tract (e.g., the esophagus, stomach and/or digestive tract) and responds to steroid therapy.
  • the methods of the present invention are useful, for example, for treating, preventing and alleviating the symptoms of eosinophilic esophagitis, inflammatory bowel diseases involving the esophagus, Crohn's disease, celiac disease, epithelial hyperplasia, basal cell hyperplasia, elongated papillae, dilated vessels in papillae, fungal esophagitis, viral esophagitis, bacterial esophagitis, corrosive esophagitis, radiation esophagitis, chemotherapy esophagitis, graft vs.
  • oral administration includes the oral administration of a solid dosage form (e.g., tablets, dragee cores, capsules, push-fit capsules, soft capsules etc.) that is formulated such that the dosage form substantially dissolves or disintegrates in the mouth and/or esophagus.
  • solid oral dosage forms are formulated such that the dosage forms substantially dissolve or disintegrate prior to reaching the stomach.
  • an oral dosage form has substantially dissolved or disintegrated if at least 50%, by weight, of the dosage form has dissolved or disintegrated. In other embodiments, substantial dissolution or disintegration includes at least 60%, 70%, 80%, 90% or 95% by weight.
  • the oral dosage form is a liquid (e.g., a slurry, suspension, syrup, dispersion, solution, etc.)
  • a patient is administered a topical corticosteroid such as, for example, budesonide.
  • a topical corticosteroid such as, for example, budesonide.
  • the inflammation treated by the methods and compositions described herein is associated with eosinophilic inflammation and/or neutrophilic inflammation.
  • individuals (e.g., patients) to be treated with compositions described herein include those that have been diagnosed eosinophilic esophagitis, an inflammatory bowel disease involving the esophagus, Crohn's disease, celiac disease, epithelial hyperplasia, basal cell hyperplasia, elongated papillae, dilated vessels in papillae, fungal esophagitis, viral esophagitis, bacterial esophagitis, corrosive esophagitis, radiation esophagitis, chemotherapy esophagitis, eosinophilic gastric outlet obstruction and related inflammation, graft vs.
  • the patient has eosinophilic esophagitis.
  • individuals e.g., patients to be treated with the compositions described herein include those that have been diagnosed with gastroesophageal reflux disease (GERD), nonerosive reflux disease (NERD) and/or erosive esophagitis.
  • GERD gastroesophageal reflux disease
  • NERD nonerosive reflux disease
  • erosive esophagitis e.g., erosive esophagitis.
  • the patient is an adult.
  • the patient is a child or infant.
  • a patient is a child or infant less than 16 years old, less than 12 years old, less than 8 years old, less than 6 years old, less than 4 years old or less than 2 years old.
  • a composition is in a unit dose formulation for oral administration of a patient.
  • a unit dose of the corticosteroid is administered from a metered dose device, such as a metered dose inhaler.
  • a metered dose device such as a metered dose inhaler.
  • from about 0.1 mg to about 20 mg, or about 0.25 to about 5 mg (e.g., about 1-2 mg/day or about 2-3 mg/day) corticosteroid per day is administered to the patient.
  • the corticosteroid is present in a unit dose in an amount of between about 0.1 mg and about 20 mg, or about 0.25 mg to about 5 mg.
  • the amount of corticosteroid administered daily or in a unit dose is between about 0.3 mg and about 4 mg.
  • the amount of corticosteroid administered daily or in a unit dose is between about 0.5 mg and about 3 mg. In other embodiments, the amount of corticosteroid present in a unit dose or administered daily is between about 1 and about 3 mg, or between about 1 and about 2 mg, or between about 2 and about 3 mg.
  • the corticosteroid is present in a pharmaceutical composition described herein in any effective amount.
  • an effective amount is an amount sufficient to reduce inflammation or symptoms of inflammation associated with an inflammatory disease or condition of the gastrointestinal tract (e.g., the esophagus) as compared to the level of inflammation or symptoms of inflammation associated with an inflammatory disease prior to administration of the effective amount.
  • effective amount is an amount sufficient to maintain a reduction in inflammation or symptoms of inflammation achieved in any manner including, but not limited to, by the administration of an effective amount sufficient to achieve such a reduction.
  • the effective amount (per day or per dose) is about 100 ⁇ g to about 20 mg, about 300 ⁇ g to about 4 mg, about 50 mg to about 500 mg, about 50 ⁇ g to about 200 mg, about 50 ⁇ g to about 100 mg, about 50 ⁇ g to about 50 mg, about 0.05 mg to about 20 mg, about 0.05 mg to about 15 mg, about 0.05 mg to about 10 mg, about 0.05 mg to about 7.5 mg, about 0.05 mg to about 5 mg, about 0.25 mg to about 3 mg, about 0.25 mg to about 2.5 mg, about 0.5 mg to about 3 mg, about 0.5 mg to about 2 mg, about 0.5 mg to about 0.1 mg, about 0.5 mg to about 5 mg, about 0.5 mg to about 4 mg, about 1 mg to about 4 mg, about 1 mg to about 3 mg, about 2 mg to about 3 mg, or about 2 mg to about 4 mg.
  • the effective amount of corticosteroid is about 0.05 mg, about 0.1 mg, about 0.15 mg, about 0.25 mg, about 0.3 mg, about 0.35 mg, about 0.4 mg, about 0.37 mg, about 0.375 mg, about 0.7 mg, about 0.8 mg, about 0.75 mg, about 1 mg, about 1.2 mg, about 1.25 mg, about 1.3 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg, about 5 mg, about 5.5 mg, about 6 mg, about 6.5 mg, about 7 mg, or about 7.5 mg or more.
  • the volume of a composition or dose of a composition described herein is an amount sufficient to substantially coat (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% of) the length of the esophagus of an individual to whom the composition is administered.
  • the volume of a composition or a dose of a composition described herein is about 0.05 mL/cm esophageal length to about 1 mL/cm esophageal length, about 0.1 mL/cm esophageal length to about 0.8 mr/cm esophageal length, about 0.2 mL/cm esophageal length to about 0.6 mL/cm esophageal length, or about 0.3 mL/cm esophageal length to about 0.5 mL/cm esophageal length, wherein the esophageal length is the esophageal length of the individual to whom the composition is administered.
  • the volume of a composition or dose of a composition described herein is based on the esophageal length of an individual (e.g., male, female, or both) that is in the 50th percentile of height for their age. Therefore, in some embodiments, the volume of a composition or dose of a composition described herein is about 0.05 mL/cm esophageal length to about 1 mL/cm esophageal length, about 0.1 mL/cm esophageal length to about 0.8 mL/cm esophageal length, about 0.2 mL/cm esophageal length to about 0.6 mL/cm esophageal length, about 0.3 mL/cm esophageal length to about 0.5 mL/cm esophageal length, about 0.32 mL/cm esophageal length to about 0.41 mL/cm esophageal length, or
  • the 50th percentile height (CDC 2000) for male children age 2 is 87 cm
  • age 3 is 95 cm
  • age 4 is 102 cm
  • age 5 is 109 cm
  • age 6 is 115 cm
  • age 7 is 122 cm
  • age 8 is 128 cm
  • age 9 is 134 cm
  • age 10 is 139 cm
  • age 11 is 144 cm
  • age 12 is 149 cm
  • age 13 is 156 cm
  • age 14 is 164 cm
  • age 15 is 170 cm
  • age 16 is 174 cm
  • age 17 is 175 cm
  • age 18 is 176 cm.
  • the amount of a therapeutic agent (e.g., a corticosteroid such as budesonide) in a composition or a dose of a composition described herein is about 0.005 mg/cm esophageal length to about 0.3 mg/cm esophageal length, about 0.008 mg/cm esophageal length to about 0.2 mg/cm esophageal length, about 0.01 mg/cm esophageal length to about 0.15 mg/cm esophageal length, or about 0.015 mg/cm esophageal length to about 0.1 mg/cm esophageal length, wherein the esophageal length is the esophageal length of the individual to whom the composition is administered.
  • a therapeutic agent e.g., a corticosteroid such as budesonide
  • the volume of a composition or dose of a composition described herein is based on the esophageal length of an individual (e.g., male, female, or both) that is in the 50th percentile of height for their age. Therefore, in some embodiments, the amount of a therapeutic agent (e.g., a corticosteroid such as budesonide) in a composition or dose of a composition described herein is about 0.005 mg/cm esophageal length to about 0.3 mg/cm esophageal length, about 0.008 mg/cm esophageal length to about 0.2 mg/cm esophageal length, about 0.01 mg/cm esophageal length to about 0.15 mg/cm esophageal length, or about 0.015 mg/cm esophageal length to about 0.1 mg/cm esophageal length, wherein the esophageal length is the esophageal length of
  • any pharmaceutical composition or dose of a pharmaceutical composition described herein is provided or administered in a volume sufficient to provide a bolus when orally administered to an individual.
  • the composition has a volume that does not systemically deliver excessive amounts of the active agent.
  • the pharmaceutical composition or dose is provided in a volume sufficient to provide a bolus when administered to an individual, wherein the size of the bolus at the distal end of the esophagus (e.g., the size of the bolus prior, e.g., immediately prior, to entering or passing the lower esophageal sphincter) is less than 90%, less than 85%, less than 80%, less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, less than 50%, less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10% or less than 5% of size of the bolus that entered the esophagus (e.g., the size of the bolus after, e.g., immediately after, passing the upper esophageal sphincter).
  • the size of the bolus at the distal end of the esophagus e.g., the size
  • the size of the bolus is determined as a measure of diameter or of volume.
  • diameter of the sphincter can be determined using gamma scintigraphy techniques.
  • the volume of the composition or dose is adjusted given the length and/or diameter of the esophagus of the individual to whom the composition or dose is administered.
  • the dose or volume of a composition administered herein is adjusted based on the efficacy of treatment.
  • a diagnosis of eosinophilic esophagitis is achieved by administering a composition described herein and determining the efficacy of the treatment.
  • a composition described herein and separately determined to be effective in treating eosinophilic esophagitis is utilized.
  • Efficacy of treatment can be determined in any suitable manner including, e.g., symptom score assessment, gastrointestinoscopy (e.g., esophagogastroduodenoscopy), gastrointestinal (e.g., esophageal) biopsy, histological evaluation, or a combination thereof.
  • Processes of diagnosing eosinophilic esophagitis and/or determining efficacy of treatment include any suitable process including, by way of non-limiting example, processes as set forth in Aceves et al., J Allergy Clin Immunol, February 2008; abstract 270, or Aceves et al., Am J. Gastroenterol., October 2007, 102(10):2271-9, both of which are incorporated herein in their entirety.
  • a process for determining efficacy of a treatment (e.g., for eosinophilic esophagitis) described herein is a clinical symptom score assessment comprising (i) administering a composition described herein to an individual diagnosed with or suspected of having eosinophilic esophagitis; and (ii) evaluating one or more symptom of the individual.
  • the process prior to administering the composition, the process comprises evaluating the one or more symptom of the individual.
  • Symptoms that are optionally scored include, by way of non-limiting example, nausea, vomiting, pain, and heartburn. Total score or change in score is optionally utilized to diagnose a disorder and/or determine efficacy of treatment.
  • a process for determining efficacy of a treatment described herein comprises (i) administering a composition described herein to an individual diagnosed with or suspected of suffering from inflammation of the gastrointestinal tract (e.g., eosinophilic esophagitis); (ii) endoscoping the gastrointestinal surface of the individual; (iii) biopsying the gastrointestinal surface tissue; and (iv) evaluating the biopsied tissue and optionally determining an endoscopy score of the tissues biopsied
  • the process further comprises comparing the evaluated biopsied tissue and/or the endoscopy score obtained prior to administration of the composition to the biopsied tissue and/or endoscopy score subsequent to administration of the composition.
  • provided herein is a process of diagnosing an individual with gastrointestinal inflammation by (i) detecting and/or measuring symptoms of the individual prior to administering to the individual a composition described herein; (ii) administering to the individual any composition described herein; (iii) detecting and/or measuring symptoms of the individual following administration of the composition; and (iv) comparing the symptoms measured or detected prior to and following administration of a composition described herein. If the symptoms exhibited by the individual are reduced (e.g., by a statistically significant or clinically relevant amount), a positive diagnosis occurs.
  • the process of diagnosing an individual with gastrointestinal inflammation is diagnosing an individual with eosinophilic esophagitis.
  • This example illustrates the increased interaction between a composition described herein and the esophagus when compared to a radiolabeled oral composition made by combining Pulmicort Respules® (4 mL) with 99m Tc pertechnetate, and diluting with saline to about 7-8 mL (M0).
  • the M0 composition has a viscosity of about 1 cP at 13.2 sec ⁇ 1 .
  • a radiolabeled budesonide composition Rosulfate, M1
  • FIG. 1 illustrates the percent amount of composition present in the esophagus as a function of time following oral administration (by measuring the amount of radiolabel present in the esophagus).
  • the area under the curve (AUCr) of the percent of the dose administered as a function of time was determined from the time of 50% swallow (i.e., 50% of the administered dose had passed from the mouth), until esophageal activity had peaked and fallen to 10% of the peak value.
  • This example details the efficacy and safety of once daily and twice daily use of budesonide formulations described herein in 5 mL, 7 mL, 10 mL, 12 mL, 15 mL, or 17.5 mL doses in inducing and maintaining remission of disease activity in children with EE.
  • a number of children e.g., 20 per budesonide dose frequency, amount, and volume
  • eos/hpf the highest eosinophil count
  • eos/hpf mean highest eosinophil count for the group.
  • Evaluation of the highest eosinophil count (eos/hpf) and the mean highest eosinophil count for the group is also determined following therapy.
  • Symptom scores and mean symptom scores are also determined before and after therapy.
  • Endoscopy is performed using the Olympus P160 endoscope (by RD) and pan-esophageal, gastric and duodenal biopsies are taken.
  • Eosinophilic esophagitis is diagnosed when ⁇ 24 eos/hpf are found in at least one of the esophageal sites biopsied.
  • Two mucosal biopsies re taken from the proximal esophagus (3 cm below the crycopharyngeus muscle), distal esophagus (3 cm above the gastroesophageal junction (GEJ), and mid-esophagus (midpoint between the crycopharyngeus muscle and the GEJ).
  • Biopsies are processed routinely and evaluated by a pediatric pathologist (RN). The highest number of eosinophils per ⁇ 400 high power field are counted. Basal zone hyperplasia (BZH) is reported when basal zone cells extend towards the luminal surface of the epithelium (>25% of epithelial thickness).
  • An EE Endoscopy Score is devised to compare findings before and after treatment. It is calculated from procedure reports and photographs. Four categories, (1) pallor and diminshed vascular markings; (2) furrowing with “thickened” mucosa; (3) white mucosal plaques; (4) concentric rings or strictures. For each category, one point is allocated if 1 or 2 esophageal sites are involved, and two points for pan-esophageal involvement. The maximum score is 8.
  • a modified symptom score based on children with acid-peptic disease is used routinely in the EE clinic.
  • the symptom categories include (1) heartburn or regurgitation; (2) abdominal pain or unexplained irritability in younger children; (3) nausea or vomiting; (4) anorexia or early satiety; (5) dysphagia or odynophagia, (6) nocturnal wakening with symptoms; (7) gastrointestinal bleeding (previous 4 months).
  • Each category scored 0-2 points with a maximum of 14 points. Zero points are awarded if the symptom is absent; one point if the symptom is mild, did not interfere with daily activities; 2 points if the symptoms are severe enough to interrupt daily activities.
  • Previous GI bleeding is considered mild (1 point) if there is no associated hemodynamic compromise or anemia, and severe (2 points) if bleeds are multiple, caused anemia, or required blood transfusion.
  • NCSS Statistical Softward Package Two-tailed p values are calculated using paired t-tests to compare the means of patient values for eos/hpf, EE Endoscopy Scores and Symptom Scores before and after budesonide therapy. Two-tailed unpaired t-tests are utilized in order to compare variables grouped by responders versus non-responders. Spearman's correlation coefficients are generated using GraphPad Prism software. Results with p values ⁇ 0.05 are considered statistically significant. Both mean and median statistics re generated, both are equivalent and mean statistics are presented.
  • Chart reviews are undertaken on a number of children. All children have >24 eos/hpf on repeat esophageal biopsy before starting therapy.
  • Treatment Patients received formulations described herein for a designated amount of time (e.g., 1 week, 2 weeks, 1 month, 2 months, 3 months, 4 months, 6 months, or the like) before repeat endoscopy.
  • Various patients received budesonide in amounts ranging from 0.25 to 2 mg/day.
  • Symptom Score Before treatment the mean symptom score for all patients is determined. It is again determined following treatment. Decreases in symptom scores (e.g., of >95%, >90%, >85%, >75%, >50%, >25%, or the like) in an individual indicate successful treatment (alone or in combination with the above referenced decreases in endoscopy scores).
  • This example details the efficacy and safety of once daily and twice daily use of budesonide in a formulation described herein in inducing and maintaining remission of disease activity in individuals (children and/or adults) with GERD.
  • Doses of 0-1 mg, 1-2 mg, 2-3 mg, 3-4 mg, 4-5 mg, and 5-6 mg per daily dose are administered once a day, b.i.d. or t.i.d. in volumes of 3, 5, 7, 10, 12, 15, or 17.5 mL.
  • a number of individuals e.g., 20 per budesonide dose frequency, amount, and volume
  • Administration is conducted for 7 days, 14 days, and 28 days.
  • Primary Outcome Measures include complete resolution of heartburn and regurgitation (e.g., no more than one day with either mild heartburn or regurgitation over the seven days prior to the assessment time-point).
  • Secondary Outcome Measures include: Number of days with heartburn (daytime and night-time); Number of days with regurgitation (daytime and night-time); Number of heartburn and regurgitation-free days (24 hrs); Composite score of heartburn and regurgitation frequency and severity; Time to resolution of symptoms of heartburn/regurgitation; Severity of additional GERD symptoms; Quality of Life (assessed using PAGI-QOL to PGIC (Patient Global Impression of Change); Complete resolution of heartburn; Complete resolution of regurgitation; Average severity of heartburn (daytime and night-time); Average severity of regurgitation (daytime and night-time). These symptoms are scored (e.g., assigning a 3 to the most severe symptoms and a 0 to a lack of symptoms) and utilized to determine the efficacy of the treatment.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nutrition Science (AREA)
  • Inorganic Chemistry (AREA)
  • Physiology (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Dispersion Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Otolaryngology (AREA)
  • Rheumatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Plant Substances (AREA)
US12/269,765 2007-11-13 2008-11-12 Compositions for the treatment of inflammation of the gastrointestinal tract Abandoned US20090149433A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/269,765 US20090149433A1 (en) 2007-11-13 2008-11-12 Compositions for the treatment of inflammation of the gastrointestinal tract

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
US98772007P 2007-11-13 2007-11-13
US1201207P 2007-12-06 2007-12-06
US1599807P 2007-12-21 2007-12-21
US1981808P 2008-01-08 2008-01-08
US3494108P 2008-03-07 2008-03-07
US3534808P 2008-03-10 2008-03-10
US5410608P 2008-05-16 2008-05-16
US5410408P 2008-05-16 2008-05-16
US5410508P 2008-05-16 2008-05-16
US5410308P 2008-05-16 2008-05-16
US5410708P 2008-05-16 2008-05-16
US9056808P 2008-08-20 2008-08-20
US12/269,765 US20090149433A1 (en) 2007-11-13 2008-11-12 Compositions for the treatment of inflammation of the gastrointestinal tract

Publications (1)

Publication Number Publication Date
US20090149433A1 true US20090149433A1 (en) 2009-06-11

Family

ID=40639386

Family Applications (5)

Application Number Title Priority Date Filing Date
US12/269,765 Abandoned US20090149433A1 (en) 2007-11-13 2008-11-12 Compositions for the treatment of inflammation of the gastrointestinal tract
US14/485,017 Active 2028-11-22 US10293052B2 (en) 2007-11-13 2014-09-12 Compositions for the treatment of gastrointestinal inflammation
US16/373,014 Active US11357859B2 (en) 2007-11-13 2019-04-02 Compositions for the treatment of gastrointestinal inflammation
US18/131,424 Abandoned US20230255984A1 (en) 2007-11-13 2023-04-06 Corticosteroid compositions
US18/533,956 Abandoned US20240108730A1 (en) 2007-11-13 2023-12-08 Corticosteroid compositions

Family Applications After (4)

Application Number Title Priority Date Filing Date
US14/485,017 Active 2028-11-22 US10293052B2 (en) 2007-11-13 2014-09-12 Compositions for the treatment of gastrointestinal inflammation
US16/373,014 Active US11357859B2 (en) 2007-11-13 2019-04-02 Compositions for the treatment of gastrointestinal inflammation
US18/131,424 Abandoned US20230255984A1 (en) 2007-11-13 2023-04-06 Corticosteroid compositions
US18/533,956 Abandoned US20240108730A1 (en) 2007-11-13 2023-12-08 Corticosteroid compositions

Country Status (23)

Country Link
US (5) US20090149433A1 (ja)
EP (7) EP2214678A2 (ja)
JP (6) JP2011503074A (ja)
KR (1) KR101245604B1 (ja)
AU (3) AU2008321030A1 (ja)
CA (5) CA2704946C (ja)
CY (2) CY1120048T1 (ja)
DK (4) DK3354276T3 (ja)
ES (5) ES2729925T3 (ja)
GB (1) GB2458403B (ja)
HK (1) HK1256861A1 (ja)
HR (2) HRP20180408T1 (ja)
HU (1) HUE038452T2 (ja)
IL (5) IL205548A0 (ja)
LT (2) LT3354276T (ja)
MX (1) MX349677B (ja)
NZ (1) NZ585268A (ja)
PL (3) PL2211896T3 (ja)
PT (4) PT3354276T (ja)
RU (1) RU2491074C2 (ja)
SI (2) SI2211896T1 (ja)
WO (5) WO2009064457A2 (ja)
ZA (1) ZA201003358B (ja)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090123390A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US20090123551A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Gastrointestinal delivery systems
US20090181099A1 (en) * 2005-11-12 2009-07-16 The Regents Of The University Of California, San Diego Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US20090264392A1 (en) * 2008-04-21 2009-10-22 Meritage Pharma, Inc. Treating eosinophilic esophagitis
US20100216754A1 (en) * 2007-11-13 2010-08-26 Meritage Pharma, Inc. Compositions for the treatment of inflammation of the gastrointestinal tract
US8324192B2 (en) 2005-11-12 2012-12-04 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US8497258B2 (en) 2005-11-12 2013-07-30 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
EP2845595A1 (en) * 2009-10-01 2015-03-11 Aptalis Pharmatech, Inc. Orally administered corticosteriod compositions
US9867834B2 (en) 2015-06-15 2018-01-16 Banner Life Sciences Llc Non-systemic topical compositions comprising corticosteroids
US9877971B2 (en) 2015-06-15 2018-01-30 Banner Life Sciences Llc Soft lozenges comprising corticosteroids
US10045946B2 (en) 2005-05-02 2018-08-14 Adare Pharmaceuticals, Inc. Timed, pulsatile release systems
US10105315B2 (en) * 2016-08-18 2018-10-23 Adare Pharmaceuticals, Inc. Methods of treating eosinophilic esophagitis
US10130580B2 (en) 2004-10-12 2018-11-20 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions
US10293052B2 (en) 2007-11-13 2019-05-21 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US10471071B2 (en) 2013-09-06 2019-11-12 Adare Pharmaceuticals, Inc. Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis
US10471017B2 (en) 2004-10-21 2019-11-12 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions with gastrosoluble pore-formers

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10809071B2 (en) * 2017-10-17 2020-10-20 AI Incorporated Method for constructing a map while performing work
CA2745930C (en) * 2008-12-08 2017-05-02 Soligenix, Inc. Topically active steroids for use in radiation and chemotherapeutics injury
EP2440210A4 (en) * 2009-06-12 2014-01-29 Meritage Pharma Inc METHOD FOR THE TREATMENT OF STOMACH DARM DISEASES
EP2515661A4 (en) * 2009-12-23 2013-11-13 Vaxgene Corp IMMUNE PROTECTION THROUGH ORAL ADMINISTRATION OF MINI-CAPSULES WITH RECOMBINANT LACTOCOCCUS LACTIS
US8865123B1 (en) 2010-09-16 2014-10-21 Mo-Sci Corporation Strontium phosphate microparticle for radiological imaging and therapy
US9849200B2 (en) 2010-09-16 2017-12-26 Mo-Sci Corporation Strontium phosphate microparticle for radiological imaging and therapy
US9119887B2 (en) 2010-09-16 2015-09-01 Mo-Sci Corporation Low-density magnesium-aluminum-silicate (MAS) microparticles for radiotherapy and/or radioimaging
EP2767286B1 (de) * 2011-10-14 2018-01-17 Obshestvo S Ogranichennoj Otvetstvennostju "CytoNIR" Orale pharmazeutische zusammensetzung zur behandlung von entzündlichen magen-darm-erkrankungen
JP5456802B2 (ja) * 2012-01-23 2014-04-02 株式会社Ｃａｃ 細胞遊走促進剤及び創傷治療用の経皮吸収剤
EP3741772B1 (en) 2012-05-08 2024-06-19 Nicox Ophthalmics, Inc. Preparations of hydrophobic therapeutic agents, methods of manufacture and use thereof
JP6423353B2 (ja) * 2012-11-09 2018-11-14 ハズ トゥー，エルエルシー 潰瘍性大腸炎の治療のための長期安定性を有する浣腸剤組成物
PL2886108T5 (pl) 2013-12-23 2023-02-27 Dr. Falk Pharma Gmbh Zoptymalizowana formulacja farmaceutyczna do leczenia zmian zapalnych przełyku
EP2886121A1 (de) 2013-12-23 2015-06-24 Dr. Falk Pharma Gmbh Wässrige Suspension enthaltend Budesonid zur Behandlung von entzündlichen Veränderungen des Ösophagus
EP3047846A1 (en) * 2015-01-22 2016-07-27 Ems S.A. Dosage forms containing fluticasone propionate for the treatment of inflammatory conditions of the esophagus
AU2017240190A1 (en) 2016-03-31 2018-09-20 Sorriso Pharmaceuticals, Inc. Compositions
GB201608276D0 (en) * 2016-05-11 2016-06-22 Abbott Lab Additive for a nutritional composition
MX2019002066A (es) * 2016-08-31 2019-06-03 Lilly Co Eli Regimen de dosificacion para el tratamiento de tumores solidos.
US20210052563A1 (en) * 2018-02-28 2021-02-25 Baylor College Of Medicine Proton pump inhibitors and methods of use in chemoradiation-induced tissue inflammation and scarring
WO2020011938A1 (en) * 2018-07-11 2020-01-16 Medizinische Universität Wien Glucocorticoids for the topical treatment of autoimmune gastritis
CN113271979A (zh) * 2018-10-24 2021-08-17 费灵有限公司 皮质类固醇的粘膜粘附性药物组合物
EP3930735A1 (en) * 2019-02-26 2022-01-05 The Regents of the University of Colorado, a body corporate Method and composition for treating gastrointestinal inflammatory disorders
EP3986931A1 (en) 2019-06-21 2022-04-27 Sorriso Pharmaceuticals, Inc. Polypeptides
AU2020294980A1 (en) 2019-06-21 2022-02-17 Sorriso Pharmaceuticals, Inc. Polypeptides
US20210330900A1 (en) * 2020-04-22 2021-10-28 Topical Sinus Therapeutics, Inc. TARGETED ADMINISTRATION TO THE OROPHARYNX OF VISCOUS OR DRY POWDER FLUTICASONE PROPIONATE AND RELATED CORTICOSTEROIDS FOR THE TREATMENT OF EOSINOPHILIC ESOPHAGITIS (EoE)
US11904046B1 (en) * 2022-11-14 2024-02-20 Eton Pharmaceuticals, Inc. Hydrocortisone oral liquid formulations

Citations (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4900552A (en) * 1988-03-30 1990-02-13 Watson Laboratories, Inc. Mucoadhesive buccal dosage forms
US5288497A (en) * 1985-05-01 1994-02-22 The University Of Utah Compositions of oral dissolvable medicaments
US5711936A (en) * 1995-06-05 1998-01-27 Whitehill Oral Technologies, Inc. Ultramulsion based ingestible compositions
US5814330A (en) * 1994-05-18 1998-09-29 Janssen Pharmaceutica, N.V. Mucoadhesive emulsions containing cyclodextrin
US5889028A (en) * 1996-02-09 1999-03-30 Mayo Foundation For Medical Education And Research Colonic delivery of nicotine to treat inflammatory bowel disease
US6291445B1 (en) * 1996-12-05 2001-09-18 Astra Aktiebolag Low dose budesonide formulations and uses thereof
US6306789B1 (en) * 1995-03-13 2001-10-23 Reckitt Benckiser Healthcare (Uk) Limited Mucoadhesive granules of carbomer suitable for oral administration of drugs
US20010049366A1 (en) * 2000-02-09 2001-12-06 Alcon Universal Ltd. Topical solution formulations containing an antibiotic and a corticosteroid
US6348502B1 (en) * 1998-06-10 2002-02-19 Reckitt & Colman Products Limited Formulations for the treatment of gastro-oesophageal reflux
US6387383B1 (en) * 2000-08-03 2002-05-14 Dow Pharmaceutical Sciences Topical low-viscosity gel composition
US6509028B2 (en) * 2000-06-26 2003-01-21 Epicept Corporation Methods and compositions for treating pain of the mucous membrane
US6562363B1 (en) * 1997-09-26 2003-05-13 Noven Pharmaceuticals, Inc. Bioadhesive compositions and methods for topical administration of active agents
US6589551B1 (en) * 1998-07-02 2003-07-08 Reckitt Benckiser Healthcare (Uk) Limited Chewable oral unit dosage
US6638521B2 (en) * 1998-08-24 2003-10-28 The Procter & Gamble Company Oral liquid mucoadhesive compositions
US20040023935A1 (en) * 2002-08-02 2004-02-05 Dey, L.P. Inhalation compositions, methods of use thereof, and process for preparation of same
US20040141949A1 (en) * 2000-11-22 2004-07-22 Rosenthal Gary J. Treatment of mucositis
US20050042282A1 (en) * 2001-12-19 2005-02-24 Eisai Co., Ltd. Methods using proton pump inhibitors
US6899099B2 (en) * 1997-12-31 2005-05-31 Astrazeneca Ab Method for treating a respiratory disease
US6916485B2 (en) * 2001-07-23 2005-07-12 Bioalliance Pharma Prolonged release bioadhesive therapeutic systems
US6923988B2 (en) * 1999-11-23 2005-08-02 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US20050239845A1 (en) * 2004-04-16 2005-10-27 Santarus, Inc. Combination of proton pump inhibitor, buffering agent, and prokinetic agent
US20060024238A1 (en) * 2002-05-17 2006-02-02 Eisai Co., Ltd. Compositions and methods using proton pump inhibitors
US7063862B2 (en) * 2003-06-03 2006-06-20 Biokey, Inc. Pharmaceutical composition and method for treating
US20060193783A1 (en) * 2003-02-17 2006-08-31 Bhowmick Balaram S Low dose corticosteroid composition
US20060235053A1 (en) * 2003-05-06 2006-10-19 Atlanta Pharma Ag Agents for the treatment of lower abdominal disorders
US20070111978A1 (en) * 2005-11-12 2007-05-17 Ranjan Dohil Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US7288267B2 (en) * 1999-10-08 2007-10-30 Elan Pharma International Ltd. Bioadhesive nanoparticulate compositions having cationic surface stabilizers
US20090123390A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US20090123551A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Gastrointestinal delivery systems

Family Cites Families (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2861920A (en) 1954-05-04 1958-11-25 Upjohn Co Therapeutic suspensions of steroids containing pvp and/or pva
US3539365A (en) 1967-02-13 1970-11-10 Fmc Corp Dispersing and stabilizing agent comprising beta-1,4 glucan and cmc and method for its preparation
US4361545A (en) 1979-05-21 1982-11-30 Rowell Laboratories, Inc. Solid pharmaceutical formulations for slow, zero order release via controlled surface erosion
JPS5762284A (en) 1980-10-01 1982-04-15 Sumitomo Chem Co Ltd Stabilizing method
US4440763A (en) 1981-03-18 1984-04-03 Block Drug Company, Inc. Use of 4-aminosalicyclic acid as an anti-inflammatory agent
US4372861A (en) * 1981-05-04 1983-02-08 Atlantic Richfield Company Graphite dispersion
US4427681A (en) 1982-09-16 1984-01-24 Richardson-Vicks, Inc. Thixotropic compositions easily convertible to pourable liquids
US4539198A (en) 1983-07-07 1985-09-03 Rowell Laboratories, Inc. Solid pharmaceutical formulations for slow, zero order release via controlled surface erosion: expanded range
US4684534A (en) 1985-02-19 1987-08-04 Dynagram Corporation Of America Quick-liquifying, chewable tablet
GB8628359D0 (en) 1986-11-27 1986-12-31 Zyma Sa Galenical formulation
GB8630913D0 (en) 1986-12-24 1987-02-04 Glaxo Group Ltd Pharmaceutical compositions
US5446070A (en) 1991-02-27 1995-08-29 Nover Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
CA1340994C (en) 1989-09-21 2000-05-16 Rudolf Edgar Dr. Falk Treatment of conditions and disease
US5643602A (en) 1989-11-22 1997-07-01 Astra Aktiebolag Oral composition for the treatment of inflammatory bowel disease
JPH04312526A (ja) 1991-04-09 1992-11-04 Fujisawa Pharmaceut Co Ltd 骨疾患治療剤
TW202387B (ja) * 1991-05-28 1993-03-21 Lilly Co Eli
US5380535A (en) 1991-05-28 1995-01-10 Geyer; Robert P. Chewable drug-delivery compositions and methods for preparing the same
DE69306379T2 (de) 1992-03-10 1997-06-12 Fisons Plc Inhalierbare arzneimittel
JPH06107550A (ja) 1992-09-29 1994-04-19 Yutaka Kurachi 経口抗炎症剤
PE44995A1 (es) 1994-01-27 1995-12-18 Schering Corp Furoato de mometasona para el tratamiento de las enfermedades pulmonares y de las vias respiratorias
AU3726395A (en) 1994-09-27 1996-04-19 Virotex Corporation Improved topical carriers for mucosal applications
US5585108A (en) 1994-12-30 1996-12-17 Nanosystems L.L.C. Formulations of oral gastrointestinal therapeutic agents in combination with pharmaceutically acceptable clays
US5763910A (en) 1995-01-31 1998-06-09 Fujitsu Limited Semiconductor device having a through-hole formed on diffused layer by self-alignment
US5679390A (en) 1995-07-27 1997-10-21 Conover; Donald Robert Composition and method for making/using a natural fat-free, deep-fried flavoring
US5863910A (en) 1996-01-12 1999-01-26 Bolonick; Joel Treatment of chronic inflammatory disorders of the gastrointestinal tract
US5840332A (en) 1996-01-18 1998-11-24 Perio Products Ltd. Gastrointestinal drug delivery system
US5855913A (en) 1997-01-16 1999-01-05 Massachusetts Instite Of Technology Particles incorporating surfactants for pulmonary drug delivery
US5985309A (en) 1996-05-24 1999-11-16 Massachusetts Institute Of Technology Preparation of particles for inhalation
CN1222317C (zh) 1996-07-12 2005-10-12 第一制药株式会社 可迅速崩解的压模物质及其生产方法
US6599927B2 (en) 1996-10-11 2003-07-29 Astrazeneca Ab Use of an H+, K+-ATPase inhibitor in the treatment of Widal's Syndrome
FR2756739B1 (fr) 1996-12-05 2000-04-28 Astra Ab Nouvelle formulation de budesonide
US5837713A (en) 1997-02-26 1998-11-17 Mayo Foundation For Medical Education And Research Treatment of eosinophil-associated pathologies by administration of topical anesthetics and glucocorticoids
US6495167B2 (en) 1997-03-20 2002-12-17 Schering Corporation Preparation of powder agglomerates
AUPO625797A0 (en) 1997-04-17 1997-05-15 Sola International Holdings Ltd Spectacles bearing sunglass lenses
WO1998050005A1 (en) * 1997-05-09 1998-11-12 Medlogic Global Corporation Compositions for cosmetic applications
DK1021171T3 (da) 1997-10-09 2003-08-25 Dexcel Pharma Technologies Ltd Lægemiddelfremførelsessystem til forsinket, fuldstændig frigivelse gastrointestinalt
SE9704186D0 (sv) * 1997-11-14 1997-11-14 Astra Ab New composition of matter
US6066292A (en) 1997-12-19 2000-05-23 Bayer Corporation Sterilization process for pharmaceutical suspensions
SE9704833D0 (sv) * 1997-12-22 1997-12-22 Astra Ab New formulation
CA2318128C (en) 1998-01-20 2008-10-14 Applied Analytical Industries, Inc. Oral liquid compositions
AU735084B2 (en) 1998-02-09 2001-06-28 Joel Bolonick Treatment of chronic inflammatory disorders of the gastrointestinal tract
US20020002154A1 (en) * 1998-02-11 2002-01-03 Pol-Henri Guivarc'h Method and composition for treatment of inflammatory conditions
DE69908304T2 (de) 1998-02-11 2004-02-19 Rtp Pharma Corp. Ungesättigte fettsäure und steroide enthaltende kombinationspräparate zur behandlung von entzündungen
US6168805B1 (en) 1998-05-07 2001-01-02 Endo Pharmaceuticals, Inc. Aqueous process for manufacturing paroxetine solid dispersions
US6071523A (en) 1998-06-03 2000-06-06 Taro Pharmaceuticals Industries, Ltd. Spill resistant pharmaceutical compositions in semi-solid form
US6241969B1 (en) * 1998-06-26 2001-06-05 Elan Corporation Plc Aqueous compositions containing corticosteroids for nasal and pulmonary delivery
US20010016577A1 (en) 1998-08-24 2001-08-23 Douglas Joseph Dobrozsi Oral mucoadhesive compositions containing gastrointestinal actives
US6319513B1 (en) 1998-08-24 2001-11-20 The Procter & Gamble Company Oral liquid mucoadhesive compounds
US6028095A (en) 1998-10-15 2000-02-22 Warner-Lambert Company Treatment of inflammatory bowel disease using histamine H3 -receptor agonists
US6635281B2 (en) 1998-12-23 2003-10-21 Alza Corporation Gastric retaining oral liquid dosage form
ES2197600T3 (es) 1999-01-29 2004-01-01 Disphar International B.V. Composiciones farmaceuticas.
US6136603A (en) 1999-03-26 2000-10-24 Isis Pharmaceuticals Inc. Antisense modulation of interleukin-5 signal transduction
GB9910212D0 (en) * 1999-05-05 1999-06-30 Reckitt & Colmann Prod Ltd Improvements in or relating to organic compositions
TWI263496B (en) * 1999-12-10 2006-10-11 Novartis Ag Pharmaceutical combinations and their use in treating gastrointestinal disorders
US6596261B1 (en) 2000-01-25 2003-07-22 Aeropharm Technology Incorporated Method of administering a medicinal aerosol formulation
WO2001063633A1 (en) 2000-02-22 2001-08-30 U S Army Inst Of Surgical Res Syringe holder attachment for attaching a syringe to a medication bottle
US20040115133A1 (en) 2000-05-10 2004-06-17 Wermeling Daniel P. Intranasal opioid compositions
US6375982B1 (en) 2000-07-05 2002-04-23 Capricorn Pharma, Inc. Rapid-melt semi-solid compositions, methods of making same and method of using same
AU2001279284A1 (en) 2000-07-05 2002-01-14 Capricorn Pharma, Inc Rapid-melt semi-solid compositions, methods of making same and methods of using same
IT1318649B1 (it) 2000-07-28 2003-08-27 Propharma S R L Ora Sinclair P Composizioni farmaceutiche per il trattamento di mucositi e stomatiti.
US6787532B2 (en) 2000-08-05 2004-09-07 Smithkline Beecham Corporation Formulation containing anti-inflammatory androstane derivatives
US6488937B1 (en) 2000-08-23 2002-12-03 William Smits Allergy treatment method using a rapid immunotherapy protocol
WO2002024205A1 (en) 2000-09-19 2002-03-28 Humanetics Corporation TREATMENT OF INFLAMMATORY BOWEL DISEASE BY THE ADMINISTRATION OF Δ5-ANDROSTENE-3β-OL-7,17 DIONE AND METABOLIZABLE PRECURSORS THEREOF
WO2002030400A1 (fr) 2000-10-06 2002-04-18 Takeda Chemical Industries, Ltd. Preparations solides
CA2423930C (en) 2000-10-27 2009-11-24 Leo Pharma A/S Topical composition containing at least one vitamin d or one vitamin d analogue and at least one corticosteroid
US20020132803A1 (en) 2001-01-05 2002-09-19 Mahendra Dedhiya Fluticasone suspension formulation, spray pattern method, and nasal spray apparatus
US7544348B2 (en) 2001-02-15 2009-06-09 Access Pharmaceuticals, Inc. Liquid formulations for the prevention and treatment of mucosal diseases and disorders
US7547433B2 (en) 2001-02-15 2009-06-16 Access Pharmaceuticals, Inc. Liquid formulations for the prevention and treatment of mucosal diseases and disorders
CN1239151C (zh) 2001-03-06 2006-02-01 协和发酵工业株式会社 口腔内快速崩解片剂
WO2002074316A1 (en) 2001-03-15 2002-09-26 Enteron Pharmaceuticals, Inc. Method of treating inflammatory disorders of the gastrointestinal tract using topical active corticosteroids
US20040156903A1 (en) 2002-05-22 2004-08-12 Abrams Andrew L.. Metering and packaging of controlled release medication
US6685971B2 (en) * 2001-06-28 2004-02-03 Rongxiang Xu Method and composition for repairing and promoting regeneration of mucosal tissue in the gastrointestinal tract
CA2409552A1 (en) * 2001-10-25 2003-04-25 Depomed, Inc. Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract
US20030129242A1 (en) 2002-01-04 2003-07-10 Bosch H. William Sterile filtered nanoparticulate formulations of budesonide and beclomethasone having tyloxapol as a surface stabilizer
SE0200657D0 (sv) 2002-03-04 2002-03-04 Astrazeneca Ab Novel Formulation
NO20024880L (no) 2002-03-19 2003-09-22 Per Hamre Sammensetning inneholdende fosfat
ES2199061B1 (es) 2002-06-10 2005-02-16 Laboratorios Vita, S.A. Comprimidos bucodispersables y procedimiento para su obtencion.
US20040258716A1 (en) 2002-06-17 2004-12-23 Shen Gao Ibuprofen suspension
US7148211B2 (en) 2002-09-18 2006-12-12 Genzyme Corporation Formulation for lipophilic agents
US8168170B2 (en) 2002-10-03 2012-05-01 The Procter And Gamble Company Compositions having an inner core and at least three surrounding layers
FR2845917B1 (fr) 2002-10-21 2006-07-07 Negma Gild Composition pharmaceutique associant le tenatoprazole et un anti-inflammatoire
JP2006507311A (ja) 2002-11-05 2006-03-02 コーセプト セラピューティクス， インコーポレイテッド 胃食道逆流性疾患を処置するための方法
SE0203410D0 (sv) 2002-11-18 2002-11-18 Astrazeneca Ab New use
EP1428526A1 (en) 2002-12-13 2004-06-16 Rijksuniversiteit Groningen Formulation for fast dissolution of lipophilic compounds
US20040121003A1 (en) 2002-12-19 2004-06-24 Acusphere, Inc. Methods for making pharmaceutical formulations comprising deagglomerated microparticles
WO2004062692A1 (en) 2003-01-13 2004-07-29 Solvay Pharmaceuticals B.V. Formulation of poorly water-soluble active substances
US20040208833A1 (en) 2003-02-04 2004-10-21 Elan Pharma International Ltd. Novel fluticasone formulations
US20040162333A1 (en) 2003-02-19 2004-08-19 Naima Mezaache Rapid absorption selective 5-HT agonist formulations
US8012505B2 (en) 2003-02-28 2011-09-06 Alk-Abello A/S Dosage form having a saccharide matrix
US7758497B2 (en) 2003-06-20 2010-07-20 Contura A/S Endoscopic attachment device
CN101005829A (zh) 2003-10-21 2007-07-25 艾克塔维斯集团公司 喹硫平制剂
US20050095271A1 (en) 2003-10-23 2005-05-05 Crank Sports, Inc. Electrolyte Energy Gel
US20050175689A1 (en) 2003-10-27 2005-08-11 Yamanouchi Pharmaceutical Co., Ltd. Coated fine particles containing drug for intrabuccally fast disintegrating tablet
GB2408937A (en) 2003-12-09 2005-06-15 Johnson & Johnson Medical Ltd pH dependent medicinal compositions
WO2005065185A2 (en) 2003-12-24 2005-07-21 Collegium Pharmaceuticals, Inc. Temperature-stable formulations, and methods of development thereof
US20070020196A1 (en) 2003-12-31 2007-01-25 Pipkin James D Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid prepared from a unit dose suspension
US20070020299A1 (en) 2003-12-31 2007-01-25 Pipkin James D Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid
WO2005074930A1 (en) * 2004-01-28 2005-08-18 Altana Pharma Ag Pharmaceutical combinations of (s) -pantoprazole with nsaid or corticosteroids
KR20070007299A (ko) 2004-01-30 2007-01-15 코리움 인터네셔널, 인크. 활성제의 전달을 위한 급속 용해 필름
US7758877B2 (en) 2004-02-05 2010-07-20 Taro Pharmaceuticals U.S.A., Inc. Stable loratadine spill resistant formulation
WO2005102287A2 (en) 2004-04-22 2005-11-03 Duocort Ab Pharmaceutical compositions for acute glucocorticoid therapy
US20050238597A1 (en) 2004-04-26 2005-10-27 Mccook John P Topical treatment of acne, seborrheic dermatitis, and oily skin with formulations containing histamine antagonists
WO2005113008A1 (en) 2004-05-21 2005-12-01 Mediplex Corp. Delivery agents for enhancing mucosal absorption of therapeutic agents
WO2005120517A1 (en) 2004-06-07 2005-12-22 Strides Arcolab Limited Stable liquid suspension formulation comprising synthetic steroids and process for producing the same
EP1768647B1 (en) 2004-06-17 2012-08-08 Virun, Inc. Compositions comprising a mucoadhesive protein and an active principle for mucosal delivery of said agent
US7858115B2 (en) 2004-06-24 2010-12-28 Idexx Laboratories Phospholipid gel compositions for drug delivery and methods of treating conditions using same
AU2005256653B2 (en) 2004-06-28 2010-10-14 Solvay Pharmaceuticals B.V. Oral sustained release formulation of tedisamil with gastric retention properties
US20060013873A1 (en) 2004-07-16 2006-01-19 Chih-Chiang Yang Bioadhesive dosage form of steroids
EP2444071A1 (en) 2004-09-27 2012-04-25 Sigmoid Pharma Limited Minicapsule formulations
ITTO20040760A1 (it) 2004-11-03 2005-02-03 Uni Degli Studi Del Piemonte Uso di un corticosteroide in associazione ad altri principi attivi per il trattamento della stenosi vascolare e la prevenzione della restenosi vascolare
JP2006158379A (ja) 2004-11-15 2006-06-22 Kao Corp 脂質燃焼促進用容器詰飲料
CA2588433A1 (en) 2004-11-17 2006-05-26 Michael R. Robinson Steroid formulation and methods of treatment using same
WO2006056066A1 (en) 2004-11-29 2006-06-01 Tir Systems Ltd. Integrated modular lighting unit
US20070134280A1 (en) 2004-12-10 2007-06-14 Roman Stephen B Thixotropic ingestible formulation to treat sore throat
WO2006065991A2 (en) 2004-12-17 2006-06-22 Dr. Reddy's Laboratories Ltd. Dispersion for delivering active agents
KR20070111497A (ko) * 2005-02-10 2007-11-21 오렉쏘 에이비 약의 경점막 투여에 유용한 새로운 약학 조성물
WO2006117803A2 (en) 2005-03-14 2006-11-09 Devarajan, Padma, Venkitachalam Transmucosal drug delivery systems
BRPI0606283A2 (pt) 2005-03-16 2009-06-09 Elan Pharma Int Ltd formulações de antagonista de receptor de leucotrieno/corticosteróide em nanopartìcula
US8003127B2 (en) 2005-03-23 2011-08-23 Elan Pharma International Limited Nanoparticulate corticosteroid and antihistamine formulations methods of making, and methods of administering thereof
WO2006103702A2 (en) * 2005-04-01 2006-10-05 Mccullough Ricky W Enhanced bio-adherent polymeric compositions for coating mucosal and epidermal epithelium
FR2884422B1 (fr) 2005-04-18 2008-04-11 Roquette Freres Composition anti-inflammatoire de l'intestin comprenant des maltodextrines branchees
CA2607250C (en) 2005-05-06 2012-11-06 Salix Pharmaceuticals, Inc. Polyethylene glycol colonic purgative composition
IL168603A (en) 2005-05-16 2011-05-31 Resdevco Res And Dev Co Pharmaceutical or cosmetic composition for the prevention and treatment of irritation of mucous cells or skin cells
US20070104785A1 (en) 2005-07-29 2007-05-10 Navale Suryakant V Tablets of linezolid form iii and processes for their preparation
US7799331B2 (en) * 2005-08-04 2010-09-21 Taro Pharmaceutical North America, Inc. Oral suspension of prednisolone acetate
CN101242811B (zh) 2005-08-15 2015-06-17 雅培实验室有限公司 酸不稳定性药物的控释药物组合物
US20070059361A1 (en) 2005-09-09 2007-03-15 University Of Manitoba Fast-disintegrating epinephrine tablets for buccal or sublingual administration
ITMI20051999A1 (it) 2005-10-21 2007-04-22 Eratech S R L Formulazioni inalatorie di farmaci in fora di polvere secca per somministrazione come tale o con nebulizzatore e dotate di elevata erogabilita' respirabilita' e stabilita'
US8497258B2 (en) 2005-11-12 2013-07-30 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US8679545B2 (en) 2005-11-12 2014-03-25 The Regents Of The University Of California Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US20070116839A1 (en) 2005-11-23 2007-05-24 The Coca-Cola Company High-Potency Sweetener Composition With C-Reactive Protein Reducing Substance and Compositions Sweetened Therewith
US20070116829A1 (en) 2005-11-23 2007-05-24 The Coca-Cola Company Pharmaceutical Composition with High-Potency Sweetener
WO2007067208A1 (en) * 2005-12-09 2007-06-14 Teva Pharmaceutical Industries Ltd. Aqueous dispersions and solutions of difficult to dissolve compounds and methods of their preparation
US20070148248A1 (en) 2005-12-22 2007-06-28 Banner Pharmacaps, Inc. Gastric reflux resistant dosage forms
WO2007096906A2 (en) 2006-02-27 2007-08-30 Panacea Biotec Ltd. Novel buccoadhesive compositions and process of preparation thereof
CA2649895C (en) 2006-04-19 2013-03-26 Novadel Pharma Inc. Stable hydroalcoholic oral spray formulations and methods
US7711383B2 (en) 2006-06-30 2010-05-04 Motorola, Inc. Method and system for communicating within a communication network
US20080161275A1 (en) 2006-12-05 2008-07-03 Resolvyx Pharmaceuticals, Inc. Compositions and methods for the treatment of inflammatory disease
WO2008091855A1 (en) 2007-01-22 2008-07-31 Novavax, Inc. Multi-phasic pharmaceutical formulations of poorly water-soluble drugs for reduced fed/fasted variability and improved oral bioavailability
ES2729925T3 (es) 2007-11-13 2019-11-07 Meritage Pharma Inc Composiciones de corticosteroides
US20100216754A1 (en) 2007-11-13 2010-08-26 Meritage Pharma, Inc. Compositions for the treatment of inflammation of the gastrointestinal tract
US20090264392A1 (en) 2008-04-21 2009-10-22 Meritage Pharma, Inc. Treating eosinophilic esophagitis
LT2328553T (lt) 2008-08-20 2020-09-10 The Regents Of The University Of California Kortikosteroidai, skirti virškinimo trakto uždegiminių ligų gydymui
EP2440210A4 (en) 2009-06-12 2014-01-29 Meritage Pharma Inc METHOD FOR THE TREATMENT OF STOMACH DARM DISEASES
CA3037273C (en) 2009-10-01 2022-05-03 Fredric Jay Cohen Orally administered corticosteroid compositions
EP3970726A1 (en) 2010-06-24 2022-03-23 ViroPharma Biologics LLC Methods of treatment for esophageal inflammation

Patent Citations (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5288497A (en) * 1985-05-01 1994-02-22 The University Of Utah Compositions of oral dissolvable medicaments
US4900552A (en) * 1988-03-30 1990-02-13 Watson Laboratories, Inc. Mucoadhesive buccal dosage forms
US5814330A (en) * 1994-05-18 1998-09-29 Janssen Pharmaceutica, N.V. Mucoadhesive emulsions containing cyclodextrin
US6306789B1 (en) * 1995-03-13 2001-10-23 Reckitt Benckiser Healthcare (Uk) Limited Mucoadhesive granules of carbomer suitable for oral administration of drugs
US5711936A (en) * 1995-06-05 1998-01-27 Whitehill Oral Technologies, Inc. Ultramulsion based ingestible compositions
US5889028A (en) * 1996-02-09 1999-03-30 Mayo Foundation For Medical Education And Research Colonic delivery of nicotine to treat inflammatory bowel disease
US6291445B1 (en) * 1996-12-05 2001-09-18 Astra Aktiebolag Low dose budesonide formulations and uses thereof
US6562363B1 (en) * 1997-09-26 2003-05-13 Noven Pharmaceuticals, Inc. Bioadhesive compositions and methods for topical administration of active agents
US6899099B2 (en) * 1997-12-31 2005-05-31 Astrazeneca Ab Method for treating a respiratory disease
US6348502B1 (en) * 1998-06-10 2002-02-19 Reckitt & Colman Products Limited Formulations for the treatment of gastro-oesophageal reflux
US6589551B1 (en) * 1998-07-02 2003-07-08 Reckitt Benckiser Healthcare (Uk) Limited Chewable oral unit dosage
US6638521B2 (en) * 1998-08-24 2003-10-28 The Procter & Gamble Company Oral liquid mucoadhesive compositions
US7288267B2 (en) * 1999-10-08 2007-10-30 Elan Pharma International Ltd. Bioadhesive nanoparticulate compositions having cationic surface stabilizers
US6923988B2 (en) * 1999-11-23 2005-08-02 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US20010049366A1 (en) * 2000-02-09 2001-12-06 Alcon Universal Ltd. Topical solution formulations containing an antibiotic and a corticosteroid
US6509028B2 (en) * 2000-06-26 2003-01-21 Epicept Corporation Methods and compositions for treating pain of the mucous membrane
US6387383B1 (en) * 2000-08-03 2002-05-14 Dow Pharmaceutical Sciences Topical low-viscosity gel composition
US20040141949A1 (en) * 2000-11-22 2004-07-22 Rosenthal Gary J. Treatment of mucositis
US6916485B2 (en) * 2001-07-23 2005-07-12 Bioalliance Pharma Prolonged release bioadhesive therapeutic systems
US20050042282A1 (en) * 2001-12-19 2005-02-24 Eisai Co., Ltd. Methods using proton pump inhibitors
US20060024238A1 (en) * 2002-05-17 2006-02-02 Eisai Co., Ltd. Compositions and methods using proton pump inhibitors
US20040023935A1 (en) * 2002-08-02 2004-02-05 Dey, L.P. Inhalation compositions, methods of use thereof, and process for preparation of same
US20060193783A1 (en) * 2003-02-17 2006-08-31 Bhowmick Balaram S Low dose corticosteroid composition
US20060235053A1 (en) * 2003-05-06 2006-10-19 Atlanta Pharma Ag Agents for the treatment of lower abdominal disorders
US7063862B2 (en) * 2003-06-03 2006-06-20 Biokey, Inc. Pharmaceutical composition and method for treating
US20050239845A1 (en) * 2004-04-16 2005-10-27 Santarus, Inc. Combination of proton pump inhibitor, buffering agent, and prokinetic agent
US20070111978A1 (en) * 2005-11-12 2007-05-17 Ranjan Dohil Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US20090123390A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US20090123551A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Gastrointestinal delivery systems
US20090123550A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Corticosteroid compositions
US20090131386A1 (en) * 2007-11-13 2009-05-21 Meritage Pharma, Inc. Compositions for the treatment of inflammation of the gastrointestinal tract
US20090143343A1 (en) * 2007-11-13 2009-06-04 Meritage Pharma, Inc. Compositions for the treatment of inflammation of the gastrointestinal tract

Cited By (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11452689B2 (en) 2004-10-12 2022-09-27 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions
US10130580B2 (en) 2004-10-12 2018-11-20 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions
US10568832B2 (en) 2004-10-12 2020-02-25 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions
US10952971B2 (en) 2004-10-21 2021-03-23 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions with gastrosoluble pore-formers
US10471017B2 (en) 2004-10-21 2019-11-12 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions with gastrosoluble pore-formers
US11147772B2 (en) 2005-05-02 2021-10-19 Adare Pharmaceuticals, Inc. Timed, pulsatile release systems
US10045946B2 (en) 2005-05-02 2018-08-14 Adare Pharmaceuticals, Inc. Timed, pulsatile release systems
US10500161B2 (en) 2005-05-02 2019-12-10 Adare Pharmaceuticals, Inc. Timed, pulsatile release systems
US9119863B2 (en) 2005-11-12 2015-09-01 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US11197822B2 (en) 2005-11-12 2021-12-14 The Regents Of The University Of California Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US8497258B2 (en) 2005-11-12 2013-07-30 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US8679545B2 (en) 2005-11-12 2014-03-25 The Regents Of The University Of California Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US20090181099A1 (en) * 2005-11-12 2009-07-16 The Regents Of The University Of California, San Diego Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US8975243B2 (en) 2005-11-12 2015-03-10 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US8324192B2 (en) 2005-11-12 2012-12-04 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US9782347B2 (en) 2005-11-12 2017-10-10 The Regents Of The University Of California Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US10272037B2 (en) 2005-11-12 2019-04-30 The Regents Of The University Of California Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US11413296B2 (en) 2005-11-12 2022-08-16 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
US20090131386A1 (en) * 2007-11-13 2009-05-21 Meritage Pharma, Inc. Compositions for the treatment of inflammation of the gastrointestinal tract
US11357859B2 (en) 2007-11-13 2022-06-14 Viropharma Biologics Llc Compositions for the treatment of gastrointestinal inflammation
US20100216754A1 (en) * 2007-11-13 2010-08-26 Meritage Pharma, Inc. Compositions for the treatment of inflammation of the gastrointestinal tract
US20090137540A1 (en) * 2007-11-13 2009-05-28 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US9050368B2 (en) 2007-11-13 2015-06-09 Meritage Pharma, Inc. Corticosteroid compositions
US20090123390A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US20090123551A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Gastrointestinal delivery systems
US8865692B2 (en) 2007-11-13 2014-10-21 Meritage Pharma, Inc Compositions for the treatment of gastrointestinal inflammation
US20090143343A1 (en) * 2007-11-13 2009-06-04 Meritage Pharma, Inc. Compositions for the treatment of inflammation of the gastrointestinal tract
US20090123550A1 (en) * 2007-11-13 2009-05-14 Meritage Pharma, Inc. Corticosteroid compositions
US10293052B2 (en) 2007-11-13 2019-05-21 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US20090264392A1 (en) * 2008-04-21 2009-10-22 Meritage Pharma, Inc. Treating eosinophilic esophagitis
EP3760187A1 (en) * 2009-10-01 2021-01-06 Adare Pharmaceuticals US, L.P. Orally administered corticosteriod compositions
TWI562779B (en) * 2009-10-01 2016-12-21 Adare Pharmaceuticals Inc Orally administered corticosteroid compositions
EP2845595A1 (en) * 2009-10-01 2015-03-11 Aptalis Pharmatech, Inc. Orally administered corticosteriod compositions
US9387167B2 (en) 2009-10-01 2016-07-12 Adare Pharmaceuticals, Inc. Orally administered corticosteroid compositions
US9486407B2 (en) 2009-10-01 2016-11-08 Adare Pharmaceuticals, Inc. Orally administered corticosteroid compositions
US11266598B2 (en) 2009-10-01 2022-03-08 Ellodi Pharmaceuticals, L.P. Orally administered corticosteroid compositions
US11246828B2 (en) 2009-10-01 2022-02-15 Ellodi Pharmaceuticals, L.P. Orally administered corticosteroid compositions
US10632069B2 (en) 2009-10-01 2020-04-28 Adare Pharmaceuticals Us, L.P. Orally administered corticosteroid compositions
US9849084B2 (en) 2009-10-01 2017-12-26 Adare Pharmaceuticals, Inc. Orally administered corticosteroid compositions
TWI594754B (zh) * 2009-10-01 2017-08-11 愛戴爾製藥股份有限公司 口服皮質類固醇組合物
CN106421797A (zh) * 2009-10-01 2017-02-22 艾戴尔医药公司 口服给予的皮质类固醇组合物
US10471071B2 (en) 2013-09-06 2019-11-12 Adare Pharmaceuticals, Inc. Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis
US11166961B2 (en) 2013-09-06 2021-11-09 Ellodi Pharmaceuticals, L.P. Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis
US11260061B2 (en) 2013-09-06 2022-03-01 Ellodi Pharmaceuticals, L.P. Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis
US10195211B2 (en) 2015-06-15 2019-02-05 Patheon Softgels, Inc. Soft lozenge compositions
US9867834B2 (en) 2015-06-15 2018-01-16 Banner Life Sciences Llc Non-systemic topical compositions comprising corticosteroids
US9877971B2 (en) 2015-06-15 2018-01-30 Banner Life Sciences Llc Soft lozenges comprising corticosteroids
US10188662B2 (en) 2015-06-15 2019-01-29 Patheon Softgels, Inc. Soft lozenge compositions
US10105315B2 (en) * 2016-08-18 2018-10-23 Adare Pharmaceuticals, Inc. Methods of treating eosinophilic esophagitis
US11026887B2 (en) 2016-08-18 2021-06-08 Ellodi Pharmaceuticals, L.P. Methods of treating eosinophilic esophagitis
US11684571B2 (en) 2016-08-18 2023-06-27 Ellodi Pharmaceuticals, L.P. Methods of treating eosinophilic esophagitis
AU2017312660B2 (en) * 2016-08-18 2023-06-29 Adare Pharmaceuticals, Inc. Methods of treating eosinophilic esophagitis
US20230414498A1 (en) * 2016-08-18 2023-12-28 Ellodi Pharmaceuticals, L.P. Methods of treating eosinophilic esophagitis
US11896710B2 (en) 2016-08-18 2024-02-13 Ellodi Pharmaceuticals, L.P. Methods of treating eosinophilic esophagitis
US12059494B2 (en) * 2016-08-18 2024-08-13 Ellodi Pharmaceuticals, L.P. Methods of treating eosinophilic esophagitis

Also Published As

Publication number Publication date
RU2010119165A (ru) 2011-11-20
EP2214679A4 (en) 2013-09-25
WO2009064457A2 (en) 2009-05-22
JP2014055171A (ja) 2014-03-27
PL2211896T3 (pl) 2018-07-31
EP3574914B1 (en) 2021-12-29
ES2660141T3 (es) 2018-03-21
PL2214679T3 (pl) 2019-09-30
CA2704957A1 (en) 2009-05-22
WO2009064460A3 (en) 2009-07-30
CA2705681A1 (en) 2009-05-22
JP2016164185A (ja) 2016-09-08
HUE038452T2 (hu) 2018-10-29
IL205711A0 (en) 2010-11-30
PT3354276T (pt) 2020-04-06
PT2211896T (pt) 2018-03-21
AU2008321396A1 (en) 2009-05-22
CY1120048T1 (el) 2018-12-12
SI3354276T1 (sl) 2020-09-30
GB2458403A (en) 2009-09-23
LT3354276T (lt) 2020-04-27
DK2214677T3 (da) 2017-11-20
US10293052B2 (en) 2019-05-21
IL253948A0 (en) 2017-10-31
AU2008321395B2 (en) 2013-03-14
CY1123126T1 (el) 2021-10-29
ES2644496T3 (es) 2017-11-29
HK1256861A1 (zh) 2019-10-04
GB2458403B (en) 2010-01-13
ES2729925T3 (es) 2019-11-07
EP3354276A1 (en) 2018-08-01
GB0911779D0 (en) 2009-08-19
LT2211896T (lt) 2018-04-10
WO2009064819A2 (en) 2009-05-22
NZ585268A (en) 2012-09-28
US20150005270A1 (en) 2015-01-01
MX2010005243A (es) 2010-08-23
KR20100087007A (ko) 2010-08-02
US20240108730A1 (en) 2024-04-04
DK2214679T3 (da) 2019-05-20
JP2018135382A (ja) 2018-08-30
HRP20200495T1 (hr) 2020-06-26
EP3574914A1 (en) 2019-12-04
EP2214677A4 (en) 2013-09-25
CA2704943A1 (en) 2009-05-22
IL205548A0 (en) 2010-12-30
AU2008321395A1 (en) 2009-05-22
ES2781949T3 (es) 2020-09-09
IL253948B (en) 2021-08-31
WO2009064458A2 (en) 2009-05-22
PT2214677T (pt) 2017-11-14
PT2214679T (pt) 2019-06-17
EP2211896A4 (en) 2013-09-25
KR101245604B1 (ko) 2013-03-21
EP2214678A2 (en) 2010-08-11
EP2214677A2 (en) 2010-08-11
DK2211896T3 (en) 2018-03-12
WO2009064458A3 (en) 2009-08-13
CA2705681C (en) 2013-06-18
IL205740A0 (en) 2010-11-30
JP6239951B2 (ja) 2017-11-29
EP2211896B1 (en) 2018-01-03
CA2704946A1 (en) 2009-05-22
ES2908290T3 (es) 2022-04-28
WO2009064417A3 (en) 2009-08-13
JP6744891B2 (ja) 2020-08-19
JP2011503074A (ja) 2011-01-27
JP2011503073A (ja) 2011-01-27
ZA201003358B (en) 2011-06-29
EP2214677B1 (en) 2017-08-30
HRP20180408T1 (hr) 2018-04-20
WO2009064457A3 (en) 2009-08-13
CA2704946C (en) 2013-09-24
US20190224324A1 (en) 2019-07-25
IL284824A (en) 2021-08-31
WO2009064819A3 (en) 2009-07-02
JP6718290B2 (ja) 2020-07-08
WO2009064460A2 (en) 2009-05-22
WO2009064417A2 (en) 2009-05-22
MX349677B (es) 2017-08-08
EP2214679B1 (en) 2019-03-27
EP2214679A2 (en) 2010-08-11
SI2211896T1 (en) 2018-04-30
CA2704949A1 (en) 2009-05-22
EP3354276B1 (en) 2020-01-01
US11357859B2 (en) 2022-06-14
EP2211896A2 (en) 2010-08-04
US20230255984A1 (en) 2023-08-17
RU2491074C2 (ru) 2013-08-27
IL205740A (en) 2017-08-31
AU2008321030A1 (en) 2009-05-22
EP2214652A2 (en) 2010-08-11
JP2011503113A (ja) 2011-01-27
PL3354276T3 (pl) 2020-09-21
DK3354276T3 (da) 2020-03-30

Similar Documents

Publication Publication Date Title
US11357859B2 (en) Compositions for the treatment of gastrointestinal inflammation
US20220331242A1 (en) Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US8865692B2 (en) Compositions for the treatment of gastrointestinal inflammation
US20220323463A1 (en) Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
CA2734763C (en) Corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract
US20220273801A1 (en) Compositions for the treatment of gastrointestinal inflammation
BRPI0820081A2 (pt) composições corticoesteróides.

Legal Events

Date Code Title Description
AS Assignment

Owner name: MERITAGE PHARMA, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PHILLIPS, ELAINE;REEL/FRAME:021940/0818

Effective date: 20081204

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION