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WO1999039699A1 - Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal - Google Patents

Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal Download PDF

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Publication number
WO1999039699A1
WO1999039699A1 PCT/US1998/002265 US9802265W WO9939699A1 WO 1999039699 A1 WO1999039699 A1 WO 1999039699A1 US 9802265 W US9802265 W US 9802265W WO 9939699 A1 WO9939699 A1 WO 9939699A1
Authority
WO
WIPO (PCT)
Prior art keywords
budesonide
oil
oral formulation
suspension
treatment
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.)
Ceased
Application number
PCT/US1998/002265
Other languages
English (en)
Inventor
Joel Bolonick
Alan Stewart
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.)
Skyepharma Canada Inc
Original Assignee
RTP 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
Priority to PCT/US1998/002265 priority Critical patent/WO1999039699A1/fr
Priority to IL13759898A priority patent/IL137598A/xx
Priority to EP98907382A priority patent/EP1052977A4/fr
Priority to KR1020007008518A priority patent/KR20010040646A/ko
Priority to JP2000530199A priority patent/JP2002502812A/ja
Priority to CNB988135329A priority patent/CN1149078C/zh
Application filed by RTP Pharma Inc filed Critical RTP Pharma Inc
Priority to CA002320087A priority patent/CA2320087C/fr
Priority to AU63200/98A priority patent/AU735084B2/en
Publication of WO1999039699A1 publication Critical patent/WO1999039699A1/fr
Priority to SE0002831A priority patent/SE0002831L/
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • 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
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4891—Coated capsules; Multilayered drug free capsule shells

Definitions

  • the present invention relates to a composition and method for treatment of chronic inflammatory disorders of the gastrointestinal tract in mammals.
  • Chronic inflammatory disorders of the gastrointestinal tract are generally grouped under the heading of inflammatory bowel disease, although the * disease can affect any part of the gastrointestinal tract from the esophagus to the large intestine.
  • Inflammatory bowel disease is of unknown etiology, although psychological, immunologic, and genetic sources have been discussed as possible etiologic factors.
  • the gastrointestinal inflammation associated with inflammatory bowel disease causes a range of symptoms of increasing severity and with a variety of intestinal and extraintestinal manifestations.
  • chronic inflammatory bowel disease ranges from mild to very severe, the more severe including colitis, characterized by an inflammatory reaction involving primarily the colonic mucosa, and Crohn's disease, characterized by inflammation throughout the gastrointestinal tract.
  • colitis characterized by an inflammatory reaction involving primarily the colonic mucosa
  • Crohn's disease characterized by inflammation throughout the gastrointestinal tract.
  • Characteristic symptoms include abdominal pain, straining, diarrhea with or without blood, fatigue, fever, and weight loss. Even the mildest of these conditions can carry obvious emotional and psychological burdens. The quality of life of an affected individual can be significantly reduced.
  • Methods of treatment of inflammatory bowel disease generally involve drug therapy directed towards the suppression of gastrointestinal inflammation.
  • adrenal corticosteroids such as prednisone and prednisolone have been found to be the most efficacious treatment of Crohn' s disease and ulcerative colitis.
  • corticosteroids in relieving the symptoms of gastrointestinal inflammation is often accompanied by unfortunate steroid side effects, including hair loss, increased water and food intake, weight gain, and immunosuppression. These systemic side effects can develop after even short-term treatment.
  • a treatment that is effective in controlling the symptoms of gastrointestinal inflammation but with minimal systemic effects has been sought.
  • budesonide a corticosteroid analogue with low systemic bioavailability
  • Budesonide has been found to be efficacious when used as an enema to treat colitis.
  • the drug has also been used in clinical trials as a treatment for Crohn 's disease.
  • Administered in place of a corticosteroid such as prednisone or prednisolone, budesonide minimizes systemic side effects associated with corticosteroid treatment.
  • the present invention provides an oral formulation for treating gastrointestinal inflammation that includes an effective amount of budesonide suspended in an edible oil, typically a vegetable oil such as avocado oil.
  • an edible oil typically a vegetable oil such as avocado oil.
  • the suspension of budesonide is encapsulated in a controlled-release coating for release in a specific portion of the gastrointestinal tract .
  • a method for treating gastrointestinal inflammation in mammals includes orally administering a composition of this invention to the mammal.
  • a composition of this invention is administered daily for about two to four weeks and the dosage is subsequently tapered, generally at about two week intervals, in response to a reduction in symptoms.
  • the reduction in dosage can be from about 1/3 to about 1/2 of the initial dosage until a minimum dose that controls symptoms is determined.
  • the present invention provides an oral formulation of budesonide for treatment of gastrointestinal inflammation.
  • the formulation effectively controls the symptoms of inflammatory bowel disease at a lower dosage than the prior art formulations, thus minimizing the side effects associated with corticosteroid treatment.
  • a method of treatment is also provided.
  • An oral formulation of this invention for treating gastrointestinal inflammation includes an effective amount of budesonide suspended in an- edible oil .
  • gastrointestinal inflammation inflammatory bowel disease
  • inflammation of the gastrointestinal tract are used interchangeably herein to mean inflammation of any portion of the gastrointestinal tract, from the esophagus to the sigmoid flexure or the termination of the colon in the rectum.
  • the inflammation can be acute, but, generally, the composition of this invention is used to treat chronic conditions.
  • Budesonide is a corticosteroid manufactured by Astra Draco (Lund, Sweden) . Budesonide is commercially
  • additional processing to ensure that all particles are of a suitably small size for preparation of a suspension can be performed.
  • Such processing can include sieving of the granules to obtain those of the desired size or further powdering or milling to minimize the presence of larger granules .
  • the budesonide is suspended in an edible oil .
  • Any edible oil is suitable for use in the formulation.
  • the oil is liquid at room temperature and somewhat below room temperature.
  • the oil is a vegetable oil.
  • fish oils and other edible animal oils also can be used.
  • Suitable edible oils include those vegetable oils that are recommended for dietary uses such as corn, safflower, olive, and avocado oils, and mixtures of such oils.
  • the oil can be selected to comport with any specific dietary guidelines. Polyunsaturated oils are preferred.
  • an oil that is palatable to the animal, such as avocado oil is conveniently used. The palatability of the oil is not of concern when the suspension is administered in an encapsulated form.
  • Budesonide is present in the formulation in an effective amount.
  • the amount needed for effective treatment varies depending on numerous well known factors such as the severity and chronicity of the disease, the species, histopathologic type, and weight of the treated animal, the length and course of treatment, the region of the gastrointestinal tract to be treated, and the responsiveness of the treated animal . Determination of an effective dose is described in detail hereinafter.
  • budesonide is suspended in the oil at a concentration of about 1 mg/ml to about 2 mg/ml . Such concentrations are suitable for administration of typical dosages required for treatment of humans and domestic animals, such as dogs and cats. The suspension is relatively viscous at concentrations much above 2 mg/ml.
  • concentrations at 2 mg/ml or less are more suitable for ease of administration. This is less of a concern when the formulation is encapsulated. At concentrations much below 1 mg/ml, larger volumes of the suspension need to be administered to achieve the effective dose for larger animals, such as large dogs or humans. Therefore, concentrations of about 1 mg/ml to about 2 mg/ml are convenient for administration and formulation of an effective dose.
  • concentrations of budesonide also are capable of being formulated as stable colloidal suspensions.
  • colloidal suspensions of budesonide at 1 mg/ml in various vegetable oils were stable at room temperature for at least four months in that no precipitation of budesonide was observed.
  • the suspension can be encapsulated in a controlled- release coating, conveniently for release in the affected organ when the inflammation is localized to a particular region of the gastrointestinal tract .
  • a controlled- release formulation directed for release in a specific portion of the gastrointestinal tract permits localized exposure to budesonide and reduces unnecessary exposure of other portions of the gastrointestinal tract to the drug, further minimizing side effects. Even when the target organ is the stomach, use of an enteric coating is beneficial in eliminating exposure of the mouth and esophagus to the drug and thus minimizing side effects.
  • the controlled-release capsules can conveniently be formulated to contain total amounts of budesonide for ease
  • capsules convenient for use in treatment of humans can contain dosages of 3 mg, 6 mg, or 9 mg of budesonide.
  • the method of treatment of the present invention includes oral administration of a suspension of budesonide in edible oil to a mammal .
  • the mammal can be a human, dog, or cat.
  • the method is also suitable for treatment of commercially valuable mammals, including domestic animals such as horses, pigs, cattle, and sheep, and rare and exotic mammals such as those in zoos.
  • the proper dosage and an appropriate dosage regimen varies depending on numerous well known factors such as the severity and chronicity of the disease, the species, his opathologic type, and weight of the treated animal, the length and course of treatment, the region of the gastrointestinal tract to be treated, and the sensitivity of the treated animal to corticosteroid treatment.
  • gastrointestinal disorders often include stomach and duodenal involvement.
  • gastrointestinal disorders mostly effect the small and large intestine, while in humans ileal and bowel involvement is most common. Since the sensitivity of humans to corticosteroids is similar to that of dogs, appropriate dosage ratios for- treatment of gastrointestinal inflammation in humans can be extrapolated from the dosages suitable for treatment of gastrointestinal inflammation in dogs.
  • Cats are as responsive to treatment with corticosteroids as dogs, but experience fewer side effects.
  • the initial dose for cats is about four times that for dogs. More specifically, cats were started on an initial dose of 0.2 mg/kg twice a day and tapered to a usual maintenance dose of 0.1 mg/kg administered every other day. Dogs were started on an initial dose of 0.05 mg/kg twice a day and tapered according to response to be drug free or maintained at a dose of 0.05 mg/kg administered every other day. Although the daily dosage was conveniently administered in two portions, a single dose of twice the amount can also be used. The dose in humans is similar to that in dogs.
  • the potency of budesonide is about 10-20 times that of prednisolone.
  • a typical dosage of budesonide in oil should thus generally be about 1/10 to 1/20 that of the dosage of prednisone or prednisolone expected to be suitable for the particular animal. Determination of initial and maintenance doses is described more fully below.
  • a relatively large initial dose is given, usually for a period of two to four weeks or longer depending on the severity of the disease.
  • a portion of the initial dose of drug fails to be absorbed due to uncontrolled diarrhea.
  • the dose is generally reduced, usually to about one-half of the initial. dose for a period of an additional two weeks to four weeks .
  • each dose must be administered for a period of a
  • each dose following the initial dose is given for at least about two weeks .
  • the intestines are palpated to determine if they are thickened or if the palpation causes or aggravates discomfort ..
  • the two keys to determining that symptoms are effectively controlled that can be asked of a patient or readily determined by the owner of an animal are the presence of a firm stool and the absence of vomiting or discomfort.
  • the treatment of gastrointestinal inflammation is idiosyncratic and adjustment of dosages of corticosteroids is well within the level, of skill.
  • the disease comes in cycles having periods of elevated symptoms at the early stages. Often, the disease is aggravated by periods of stress at any stage of the disease. In the early stages, symptoms are often intermittent, and administering an effective form of- therapy may be difficult. Later, the cycles tend to cease, and the symptoms are present consistently. Often a maintenance dose must be administered daily in the later stages of the disease.
  • the formulation of this .invention is prepared by well known methods.
  • budesonide is suspended in an edible oil by adding the amount of budesonide necessary for the desired concentration to the selected oil and shaking or otherwise admixing the preparation until a suspension is achieved.
  • the suspension is a stable colloidal suspension.
  • a colloidal suspension can be prepared by hand or mechanical shaking of the drug in oil for a period of two minutes for a concentration of 1 mg/ml without any initial processing of budesonide as obtained from the manufacturer.
  • the suspension can be encapsulated by standard techniques. Techniques for encapsulation are well known and are described in
  • EXAMPLE 1 A clinical trial of the formulation of this invention for treatment of gastrointestinal inflammation was performed at a veterinary hospital . The study was conducted on dogs and cats with inflammations of the gastrointestinal tract which were diagnosed as forms of inflammatory bowel disease using endoscopy and biopsy. The study was performed as described below.
  • the formulation was powdered budesonide (Sigma Chemical Company; St. Louis, MO; Catalog No. B-7777) suspended in either avocado oil or safflower oil at a concentration of 1 mg/ml.
  • avocado oil was chosen originally because of its palatability to cats. However, one cat developed a sensitivity to avocado oil and safflower oil was substituted.
  • the drug was weighed out in small quantities (approximately 40 mg) , added to a centrifuge tube, and sufficient oil (for 40 ml total volume) was added to make the desired concentration of 1 mg/ml .
  • the tube was then vigorously shaken until all the material was completely suspended. On standing, a small percentage of the total material may have settled out and required additional shaking to resuspend. This was attributed to the variation in size of particles in the original powder, with the heavier particles not entering a truly colloidal phase. In general, not more than about 5% of the powdered budesonide settled out after the initial suspension was prepared.
  • Cats were started on an initial dose of 0.2 mg/kg twice a day.
  • the dose was tapered according to the response, usually being maintained at 0.1 mg/kg every other day.
  • the dosages were tapered after two to four weeks.
  • Dogs were started at 0.05 mg/kg twice a day.
  • the dose was also tapered according to response, the animals ultimately being maintained drug free or on a dose of 0.05 mg/kg every other day.
  • the suspension was administered to animals either directly into the mouth via a syringe or by simply allowing the animal to eat a measured amount of the drug alone or with food.
  • the clinical trial of the formulation was begun with a single cat having severe inflammatory gastric and intestinal disease. By about seven months later, a total of 2 dogs and 8 cats had been enrolled in the study. All animals had previously been medicated with prednisone or prednisolone. The average starting dose for prednisone or prednisolone was 1 mg/kg orally twice a day, which was tapered depending on the animal ' s response .
  • the animals were chosen for the- budesonide oil suspension study based on one or more of the following reasons: insufficient control of symptoms by prednisolone; side effects of prednisolone; and concurrent diseases making the use of systemic steroids undesirable, including diabetes, immunosuppression, viral infections, and pancreatitis .
  • the pets' owners were asked to rate the budesonide in oil suspension treatment in comparison to prior treatment with prednisolone and in comparison to no treatment and to rate use of prednisolone in comparison to no treatment, rating the treatment from much worse to much improved. More specifically, the treatment was rated as much worse (scored as -3) ; moderately worse (scored
  • the budesonide formulation was a significant improvement over prednisone and prednisolone for the treatment of inflammatory bowel disease in dogs and cats. This improvement was attributed to both greater potency of the formulation and fewer associated side effects.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une formulation orale pour le traitement d'inflammations gastro-intestinales, formulation qui comprend une quantité efficace de budésonide suspendu dans de l'huile alimentaire, normalement de l'huile végétale. Un procédé de traitement d'inflammations gastro-intestinales chez les mammifères fait aussi l'objet de cette invention et consiste à administrer par voie orale une composition de cette invention à un mammifère. Selon un mode de réalisation, un dosage initial est administré quotidiennement pendant environ deux à quatre semaines, après quoi le dosage est échelonné normalement à intervalles d'environ deux semaines, en réaction à une réduction des symptômes jusqu'à ce que l'on atteigne une dose minimale qui soit en mesure de supprimer les symptômes.
PCT/US1998/002265 1998-02-09 1998-02-09 Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal Ceased WO1999039699A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
IL13759898A IL137598A (en) 1998-02-09 1998-02-09 Oral formulations for treatment of chronic inflammatory disorders of the gastrointestinal tract
EP98907382A EP1052977A4 (fr) 1998-02-09 1998-02-09 Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal
KR1020007008518A KR20010040646A (ko) 1998-02-09 1998-02-09 위장관의 만성 염증성 질환의 치료방법
JP2000530199A JP2002502812A (ja) 1998-02-09 1998-02-09 胃腸管の慢性炎症疾患の治療
CNB988135329A CN1149078C (zh) 1998-02-09 1998-02-09 治疗慢性胃肠道炎症的制剂
PCT/US1998/002265 WO1999039699A1 (fr) 1998-02-09 1998-02-09 Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal
CA002320087A CA2320087C (fr) 1998-02-09 1998-02-09 Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal
AU63200/98A AU735084B2 (en) 1998-02-09 1998-02-09 Treatment of chronic inflammatory disorders of the gastrointestinal tract
SE0002831A SE0002831L (sv) 1998-02-09 2000-08-07 Behandling av kroniska inflammatoriska sjukdomar i mag-tarmkanalen

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1998/002265 WO1999039699A1 (fr) 1998-02-09 1998-02-09 Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal

Publications (1)

Publication Number Publication Date
WO1999039699A1 true WO1999039699A1 (fr) 1999-08-12

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PCT/US1998/002265 Ceased WO1999039699A1 (fr) 1998-02-09 1998-02-09 Traitement de troubles inflammatoires chroniques du tractus gastro-intestinal

Country Status (9)

Country Link
EP (1) EP1052977A4 (fr)
JP (1) JP2002502812A (fr)
KR (1) KR20010040646A (fr)
CN (1) CN1149078C (fr)
AU (1) AU735084B2 (fr)
CA (1) CA2320087C (fr)
IL (1) IL137598A (fr)
SE (1) SE0002831L (fr)
WO (1) WO1999039699A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MD2852C2 (ro) * 2005-03-28 2006-04-30 Георге АНГЕЛИЧ Utilizarea budesonidei pentru tratamentul ascitei rezistente la pacienţii cu ciroză hepatică
US8309138B2 (en) 2007-02-16 2012-11-13 Aska Pharmaceutical Co., Ltd. Pharmaceutical composition comprising microparticle oily suspension
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
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
US8865692B2 (en) 2007-11-13 2014-10-21 Meritage Pharma, Inc Compositions for the treatment of gastrointestinal inflammation
EP2214677B1 (fr) 2007-11-13 2017-08-30 Meritage Pharma, Inc. Compositions pour le traitement de l'inflammation des voies gastro-intestinales

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100333727C (zh) * 2004-11-25 2007-08-29 天津药业研究院有限公司 布地奈德靶向微丸及其制备方法

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US5674860A (en) * 1991-12-18 1997-10-07 Astra Aktiebolag Combination of a bronchodilator and a steroidal anti-inflammatory drug for the treatment of respiratory disorders

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US5643602A (en) * 1989-11-22 1997-07-01 Astra Aktiebolag Oral composition for the treatment of inflammatory bowel disease
GB9405304D0 (en) * 1994-03-16 1994-04-27 Scherer Ltd R P Delivery systems for hydrophobic drugs
GB9409778D0 (en) * 1994-05-16 1994-07-06 Dumex Ltd As Compositions
GB9412394D0 (en) * 1994-06-21 1994-08-10 Danbiosyst Uk Colonic drug delivery composition
EP0919228A4 (fr) * 1996-08-02 2001-12-12 Hisamitsu Pharmaceutical Co Gelules destinees a des preparations orales et preparations de gelules destinees a une administration orale
KR100219918B1 (ko) * 1997-07-03 1999-09-01 김윤 대장선택적 약물전달용 조성물

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
US5674860A (en) * 1991-12-18 1997-10-07 Astra Aktiebolag Combination of a bronchodilator and a steroidal anti-inflammatory drug for the treatment of respiratory disorders

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MD2852C2 (ro) * 2005-03-28 2006-04-30 Георге АНГЕЛИЧ Utilizarea budesonidei pentru tratamentul ascitei rezistente la pacienţii cu ciroză hepatică
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
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
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
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
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
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
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
US8309138B2 (en) 2007-02-16 2012-11-13 Aska Pharmaceutical Co., Ltd. Pharmaceutical composition comprising microparticle oily suspension
EP2214677B1 (fr) 2007-11-13 2017-08-30 Meritage Pharma, Inc. Compositions pour le traitement de l'inflammation des voies gastro-intestinales
US10293052B2 (en) 2007-11-13 2019-05-21 Meritage Pharma, Inc. Compositions for the treatment of gastrointestinal inflammation
US9050368B2 (en) 2007-11-13 2015-06-09 Meritage Pharma, Inc. Corticosteroid compositions
US11357859B2 (en) 2007-11-13 2022-06-14 Viropharma Biologics Llc Compositions for the treatment of gastrointestinal inflammation
US8865692B2 (en) 2007-11-13 2014-10-21 Meritage Pharma, Inc Compositions for the treatment of gastrointestinal inflammation

Also Published As

Publication number Publication date
JP2002502812A (ja) 2002-01-29
CA2320087C (fr) 2006-12-19
EP1052977A4 (fr) 2006-07-12
CA2320087A1 (fr) 1999-08-12
EP1052977A1 (fr) 2000-11-22
SE0002831D0 (sv) 2000-08-07
AU6320098A (en) 1999-08-23
KR20010040646A (ko) 2001-05-15
CN1284869A (zh) 2001-02-21
CN1149078C (zh) 2004-05-12
IL137598A0 (en) 2001-07-24
SE0002831L (sv) 2000-09-28
AU735084B2 (en) 2001-06-28
IL137598A (en) 2005-09-25

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