CN1284869A - Treatment of chronic inflammatory disorders of gastrointestinal tract - Google Patents
Treatment of chronic inflammatory disorders of gastrointestinal tract Download PDFInfo
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- CN1284869A CN1284869A CN98813532A CN98813532A CN1284869A CN 1284869 A CN1284869 A CN 1284869A CN 98813532 A CN98813532 A CN 98813532A CN 98813532 A CN98813532 A CN 98813532A CN 1284869 A CN1284869 A CN 1284869A
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- Prior art keywords
- budesonide
- oil
- oral formulations
- treatment
- suspension
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—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
Abstract
The present disclosure relates to an oral formulation for treating gastrointestinal inflammation that includes an effective amount of budesonide suspended in an edible oil, typically a vegetable oil. A method for treating gastrointestinal inflammation in mammals is also described and includes orally administering a composition of this invention to a mammal. In one embodiment, an initial dosage 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 until a minimum dose that controls symptoms is achieved.
Description
Background of invention
Invention field
The present invention relates to be used for the treatment of the compositions and the method for mammal chronic inflammatory disorders of gastrointestinal tract.
Prior art
Chronic inflammatory disorders of gastrointestinal tract is in one group of inflammatory bowel usually, although this disease can influence any position of gastrointestinal from the esophagus to the large intestine.The etiology of inflammatory bowel it be unclear that, but thinks that the reason on psychology, immunology and the genetics is possible paathogenic factor.The gastrointestinal inflammation relevant with inflammatory bowel can cause symptom that a series of orders of severity increase progressively and with multiple intestinal and the outer performance of intestinal.
The performance of chronic inflammatory intestinal diseases can be from very weak to very serious, and more serious performance comprises colitis, it is characterized in that relating generally to the inflammatory reaction of mucous membrane of colon, and Crohn disease, it is characterized in that whole gastrointestinal inflammation.The Clinical symptoms of ulcerative colitis and Crohn disease can be identical.Distinctive symptom comprise abdominal pain, strain, hemorrhage or not hemorrhagic diarrhea, fatigue, have a fever and lose weight.In these diseases, even the lightest disease also can cause tangible emotion and psychological burden.The quality of life of diseased individuals can obviously descend.
The Therapeutic Method of inflammatory bowel generally includes and is used to suppress gastrointestinal inflammatory pharmacotherapy.In anti-inflammatory drug, found that adrenocortical steroid such as prednisone and andrographolide are treatment Crohn disease and the most effective medicine of ulcerative colitis.But, corticosteroid effectively alleviate the gastrointestinal inflammation symptom often also with disadvantageous steroidal side effect, comprise picked-up increase, weight increase and the immunosuppressant of alopecia, water and food.Even the side effect of these generals also may take place behind short term therapy.Therefore, people begin to seek and can effectively control gastrointestinal inflammatory symptom and the very little Therapeutic Method of the influence of general.
Studied budesonide recently, the similar thing of corticosteroid that a kind of general bioavailability is lower is used for the treatment of the effectiveness of inflammatory bowel.Found and budesonide can have been treated colitis [Lofberg etc., diet pharmacology and therapy (AlimentaryPharmacology and Therapeutics), 8 (6): 623-629 (1994)] effectively as enema.This medicine also is used for the treatment of Crohn disease in clinical trial.Replacing corticosteroid such as prednisone or andrographolide to carry out administration with budesonide can make the systemic side effects relevant with corticosteroid treatment reduce to minimum.
Nearest clinical trial [Rutgeerts etc., New England Journal of Medicine (The NewEngland Journal of Medicine), 331 (13): 842-845 (1994)] effectiveness and the safety in the treatment Crohn disease compares to budesonide and andrographolide.With the form administration of granular budesonide, earlier with 8 weeks of dosed administration of 9mg/ days, then with 2 weeks of dosed administration of 6mg/ days with the controlled release capsule that is used for discharging at ileum.Compare with the experimenter with the andrographolide treatment, the experimenter who treats with budesonide shows less systemic side effects and less adrenal gland's inhibition.But, find that budesonide is lower than andrographolide on the effectiveness that alleviates the Crohn disease symptom.
The research budesonide treatment in the Crohn disease effectiveness and other clinical trial [Greenberg etc. of safety, New England Journal of Medicine (The New England Journal ofMedicine), 331 (13): 836-841 (1994)] in, subject group accept every day total amount be 3,9 or 15mg twice every day dosage.Described dosage is to be included in the dosage form administration of the budesonide microparticle that is used for the controlled release gelatine capsule that discharges at ileum.Discovery 9mg such as Greenberg are the minimum effective doses of alleviating Crohn disease.Greenberg etc. also find, under this dosage, although the order of severity of the side effect relevant with steroidal is lower than prednisone, still have the experimenter of significant proportion to have these side effect.
People are still seeking the Therapeutic Method that can effectively treat gastrointestinal inflammation and can effectively alleviate the systemic side effects relevant with corticosteroid treatment simultaneously.
Summary of the invention
The invention provides and be used for the treatment of gastrointestinal inflammatory oral formulations, said preparation contains the budesonide that is suspended in the effective dose in edible oil, particularly vegetable oil such as the American Avocado Tree oil.In one embodiment of the invention, the suspension of budesonide is encapsulated in the controlled release coat that is used in the release of gastrointestinal specific part.
The present invention also provides the method for treatment mammal gastrointestinal inflammation.This method comprises to mammal oral administration compositions of the present invention.In one embodiment, then according to the alleviating of symptom gradually reduce dosage with initial dose administration about 2-4 week every day, is the interval with about two weeks usually.The minimizing of dosage can from initial dose about 1/3 to about 1/2, until the minimum dose of determining controlling symptoms.
Detailed Description Of The Invention
The invention provides the oral formulations that is used for the treatment of gastrointestinal inflammatory budesonide.Said preparation can be controlled the symptom of inflammatory bowel effectively under the dosage lower than prior art preparation, thereby makes the side effect relevant with corticosteroid treatment reduce to minimum.The present invention also provides Therapeutic Method.
Be used for the treatment of gastrointestinal inflammatory oral formulations of the present invention and contain the budesonide that is suspended in the effective dose in the edible oil.Term used herein " gastrointestinal inflammation ", " inflammatory bowel " and " gastrointestinal tract inflammation " can use the inflammation with any position of gastrointestinal tract of the distal colon representing from esophagus to sigmoid colon bending or rectum each other interchangeably.Inflammation can be acute, but compositions of the present invention is generally used for treating chronic disease.
Budesonide is by Astra Draco (Lund, Sweden) corticosteroid of Sheng Chaning.Budesonide can buy with the form of particulate powder, and this powder need not further be processed and can be suspended in the oil.But, can further process to guarantee that all granules all have the little granularity that is suitable for supending.Described processing comprises sieves granule to obtain to have the granule of desired particle size, and perhaps further efflorescence or grinding are so that oarse-grained amount reduces to minimum.
Budesonide is suspended in the edible oil.Any edible oil all is applicable to said preparation.Usually, described oil is liquid under room temperature and the temperature a little less than room temperature.Preferred oil is vegetable oil.But fish oil and other edible animal oil also can use.Suitable edible oil comprises to be recommended to be used for vegetable oil such as Semen Maydis oil, safflower oil, olive oil and the American Avocado Tree oil that diet is used, and the mixture of described oil.Selection to oil can be consistent with any specific diet index.Preferred polyunsaturated oil.When placing suspension on the food or food dish during, preferably adopt oil such as the American Avocado Tree oil agreeable to the taste to animal to the animals administer of being treated.When suspension during with the form administration sealed, be need not to consider the palatability of oil.
Budesonide is present in the preparation with effective dose.Effectively the required amount of treatment changes for example reaction of body weight, the length of the course of treatment and the process of the order of severity of disease and chronicity, kind, histopathology type and the animal for the treatment of, the gastrointestinal position that will treat and the animal for the treatment of according to multiple known factor.Below will describe determining of effective dose in detail.
Preferably budesonide is suspended in the oil to the concentration of about 2mg/ml with about 1mg/ml.Described concentration is suitable for treating the administration of people and domestic animal dosage as Canis familiaris L. and cat are required.Suspension thickness comparatively when concentration is higher than 2mg/ml.Therefore, 2mg/ml or lower concentration are easy to administration.But when preparation is the form of sealing, less consideration this point.When concentration during far below 1mg/ml, the suspension that then needs the administration larger volume is to obtain the effective dose than large animal such as large-scale Canis familiaris L. or people.Therefore, about 1mg/ml to the concentration of about 2mg/ml for the administration of effective dose with prepare and suit.
In addition, the budesonide of this concentration can also be mixed with stable soliquid.Specifically, the soliquid of the 1mg/ml of budesonide in each vegetable oil can at room temperature be stablized 4 months and can not separate out budesonide at least.
When inflammation is confined to the gastrointestinal specific region, this suspension can be encapsulated in the controlled release coat that is used for discharging medicine at the organ that infects.Be used for to limit to the contact of budesonide and reducing the unnecessary contact of other position of gastrointestinal tract, thereby further reduced side effect medicine at the controlled release preparation that the gastrointestinal tract specific part discharges.Even when target organ is stomach, uses enteric coating also can advantageously eliminate contacting of oral cavity and esophagus and medicine, thereby make side effect reduce to minimum.Controlled release capsule can be mixed with easily contain total amount budesonide to be easy to required mammal administration.For example, the capsule that is usually used in the human treatment can contain the budesonide that dosage is 3mg, 6mg or 9mg.
Therapeutic Method of the present invention comprises to the suspension of mammal oral administration budesonide in edible oil.In this application, mammal can be the people, Canis familiaris L. or cat.In addition, this method also comprises and is suitable for treating the animal with commercial value, comprises tame pack animal, pig, cattle and sheep, and rare and external mammal those in the zoo for example.
Appropriate dosage and suitable dosage regimen change according to multiple known factor, for example body weight, the length of treatment time and the process of the order of severity of disease and chronicity, kind, histopathology type and the animal for the treatment of, the gastrointestinal position that will treat and the animal for the treatment of to the sensitivity of corticosteroid.For example, the gastrointestinal disease of cat involves the harmonization of the stomach duodenum usually.The gastrointestinal disease of Canis familiaris L. mainly influences small intestinal and large intestine, and people's ileum and intestinal is the most normal involves.Because the people is similar to the sensitivity and the Canis familiaris L. of corticosteroid, therefore, being used for the treatment of the gastrointestinal inflammatory optimal dose ratio of people can obtain from being used for the treatment of the gastrointestinal inflammatory optimal dose extrapolation of Canis familiaris L..
Cat is similar to Canis familiaris L. to the reaction of corticosteroid treatment, but the side effect of experience is less.Usually, the initial dose of cat approximately is 4 times of Canis familiaris L..More particularly, cat is gradually reduced to the conventional maintenance dose of per two days 0.1mg/kg then since the initial dose of twice 0.2mg/kg every day.Canis familiaris L. is since the initial dose of twice 0.05mg/kg every day, stops administration gradually according to the reaction to medicine then or maintains the dosage of per two days 0.05mg/kg.Although, also can adopt the single-dose of doubling dose preferably with the administration at twice of dosage every day.People's dosage is similar to Canis familiaris L..
In order to determine, can adopt comparison with the relative dosage of other corticosteroid to other mammiferous initial dose.Specifically, the effectiveness of budesonide approximately be andrographolide about 10-20 doubly.Therefore, the general dosage of budesonide oil suspension should be expection be suitable for the prednisone of particular animals or andrographolide dosage about 1/10 to 1/20.Determining of initial dose and maintenance dose below will more fully be described.
As known in the gastrointestinal inflammation in treatment, usually according to the order of severity of disease with 2 to 4 week or the longer times of relatively large initial dose administration.Specifically, because the diarrhoea of failing to control causes a part of medicine of initial dose to be absorbed.When that part of agents alleviate that the symptom of disease is absorbed, whole effectiveness of medicine begin to show.Then dosage is reduced, usually reuse two to around time decreased only about half of to initial dose.
But, also can adopt less reduction, for example reduce 1/3, particularly after having passed through one or many minimizing dosage.If the dosage that reduces does not cause the reproduction of symptom, then can further reduce dosage.If symptom is reappeared, then can repeat early stage dosage, reduce dosage with less ratio then.If the dosage that reduces is 2-4 week effectively, then can attempt further reducing dosage.As everyone knows, essential one week or the longer time of administration of each dosage because high dose can be after withdrawal controlling symptoms a couple of days.Preferably with each dosed administration behind the initial dose at least about 2 weeks.
In order to measure the effectiveness of drug dose clinically, intestinal is carried out palpation, and whether thickening or palpation can cause or aggravate discomfort to measure intestinal.Can inquire the patient or being used to of determining easily confirm that two clues that symptom is effectively controlled are that the stool of shaping and not vomiting or uncomfortable are arranged by the owner of animal.
Gastrointestinal inflammatory treatment is the individual specificity, is that the technical staff knows to the adjusting of corticosteroid dosage.But this disease periodically occurs usually, in the period that sx is arranged in early days in cycle.Usually, in any period of disease, pressure all can make disease increase the weight of.In early days, symptom is normally intermittent, therefore is difficult to give effective treatment.Then, the cycle trends towards stopping, and symptom continues to occur.Usually must give maintenance dose every day the late period in disease.
Preparation of the present invention can prepare by known method.Specifically, join in the selected oil jolting then by the budesonide that will reach the ideal concentration aequum or mix preparation is suspended in budesonide in the edible oil until forming suspension.Usually, suspension is stable soliquid.Specifically, soliquid can need not the budesonide of buying from manufacturer is carried out any processing in advance by concentration in oil the manual or mechanical jolting of medicine with 1mg/ml was prepared in 2 minutes.Suspension is stable once making, and need not special preservation.
After making suspension, it can be sealed by routine techniques.Wrapper technology is known, and is recorded in volumes such as Remington ' s Pharmaceutical Sciences[Gennaro, Remington ' s Pharmaceutical Sciences, the 18th edition, 1658-1664 (1990)].In addition, be used for being recorded in Greenberg etc., New England Journal of Medicine (The New England Journal of Medicine) 331 (13): 836-841 (1994) at the preparation of intestinal release budesonide; Rutgeerts etc., New England Journal of Medicine (The New England Journalof Medicine) 331 (13): 842-845 (1994); With Reynolds etc., digestive disease (Digestive Diseases), 11:334-342 (1993).
Be appreciated that according to instruction of the present invention, technology of the present invention be applied to concrete problem or situation is that those of ordinary skills know.Below will provide the example and the separation thereof of product of the present invention, the exemplary process of using and producing, but should not be seen as limitation of the invention.The embodiment that provides with past tense in fact has been used for practice.The embodiment that provides with present tense constructively is used for practice.During all documents that this paper quoted all are incorporated herein as a reference.
Embodiment 1
In veterinary hospital preparation for treating gastrointestinal inflammation of the present invention has been carried out clinical trial.Study with Canis familiaris L. that suffers from gastrointestinal tract inflammation and cat, described inflammation is diagnosed as inflammatory bowel disease through splanchnoscopy and biopsy.Study according to following description.
Preparation
Preparation is that the concentration that is suspended in American Avocado Tree oil or the safflower oil is budesonide powder (the Sigma Chemical Company of 1mg/ml; St.Louis, MO; Catalog number (Cat.No.) B-7777).The initial American Avocado Tree oil of selecting is because of its palatability to cat.But, a cat is arranged to American Avocado Tree oil allergy, so changed safflower oil into.Take by weighing small amount of drug (about 40mg), join in the centrifuge tube, add enough oil (cumulative volume 40ml) then to reach the concentration of required 1mg/ml.
Then the violent jolting of centrifuge tube is all suspended until all substances.When leaving standstill, may have that small amount of matter settles down and need jolting once more to suspend again.This be since in the starting powder difference of granularity cause, heavier granule can not enter gel phase veritably.Usually, after making initial suspension, have and be no more than about 5% budesonide powder and settle down.
Administration
The initial dose of twice 0.2mg/kg begins the cat administration with every day.Reduce dosage gradually according to reaction, maintain per two days 0.1mg/kg usually.Reduce dosage after week gradually at 2-4.Twice 0.05mg/kg begins the Canis familiaris L. administration with every day.Reduce dosage gradually according to reaction equally, stop animals administer at last or maintain the dosage of per two days 0.05mg/kg.With suspension by directly delivering in the mouth with syringe or making animal carry out administration separately or with the edible true quantitative medicine of food simply.
Clinical data
During beginning, carry out the clinical trial of preparation with a cat that suffers from serious inflammatory gastrointestinal disease.After about 7 months, have the registration of 2 Canis familiaris L.s and 8 cats and entered research.All animals were all treated with prednisone or andrographolide in the past.The average initial dose of prednisone or andrographolide is 1mg/kg, and every day, oral administration twice, and the reaction according to animal reduces dosage gradually then.
Select animal to be used for the research of budesonide oil suspension based on following one or more reasons: andrographolide is controlling symptoms fully; The side effect of andrographolide; Bring inconvenience and use the concurrent disease of general steroid, comprise diabetes, immunosuppressant, viral infection and pancreatitis.
After bringing into use the budesonide oil suspension, all animals were all observed 6 months at least, have only a cat owing to incoherent reason has been implemented euthanasia by other veterinary clinic.What treatment time was the shortest is 2 months, and the longest is 6 months.Owner to all medication animals issues a questionnaire under study for action, continues about 4 months.The information that the application form inquiry is relevant with treatment.Application form comprises objective criterion (frequency of vomiting and the quality of feces) and more subjective standard (being easy to administration, appetite, energy level and total comfortableness).The owner who requires house pet to the treatment of budesonide oil suspension with in the past with the comparison of andrographolide treatment and with untreated trade-off grade; and to using andrographolide and untreated trade-off grade, to the classification of treatment from very bad to improvement greatly.More particularly, treatment is classified as very bad (scoring is-3); Worse (scoring is-2); Bad (scoring is-1); Do not change (scoring is 0); Slightly improve (scoring is 1); Moderate is improved (scoring is 2) and is improved (scoring is 3) greatly.
Average score tabulation to projects.The result is as shown in table 1 below.
Table 1
Andrographolide and budesonide and budesonide and project relatively are easy to administration NA without the comparison of medicine without the comparison andrographolide of medicine
*NA
*2.0 total comfortableness 0.0 2.2 2.1 vomiting frequency 1.2 1.9 1.2 stool qualities 0.6 1.8 1.7 energy level-0.1 1.6 1.9 appetite 0.0 1.5 1.6
NA
*: inapplicable (not inquiring this information)
According to scoring as can be seen, for the inflammatory bowel of treatment Canis familiaris L. and cat, budesonide formulation has clear improvement than prednisone and andrographolide.It is stronger and related side effects is less that this improves effectiveness owing to preparation.
Studies confirm that the suspension preparation of budesonide in edible oil not only makes side effect than the obvious minimizing of andrographolide, and the effectiveness of control disease is better than andrographolide and is mixed with other budesonide formulation except that oil suspension.
Embodiment 2
With other preparation a cat and a Canis familiaris L. are tested, but the result is more very different than vegetable oil preparation.A kind of preparation is the suspension of budesonide (being similarly 1mg/ml) in 40% glycerol, 60% water.Another kind of carrier is 10% Polyethylene Glycol (molecular weight 800) and 90% water, is suspended with the budesonide of 1mg/ml therein.In both cases, budesonide looks and all can evenly suspend, forms milky suspension.But the effectiveness of two kinds of preparations is more very different than vegetable oil preparation, so that no longer be suitable for continuing to use animal is treated according to the description of embodiment 1.
Claims (17)
1. one kind is used for the treatment of gastrointestinal inflammatory oral formulations, and said preparation contains the suspension of budesonide in edible oil of effective dose.
2. the oral formulations of claim 1, wherein the concentration of budesonide is about 1.0-2.0mg/ml.
3. the oral formulations of claim 1, suspension wherein is a soliquid.
4. the oral formulations of claim 1, edible oil wherein is a polyunsaturated oil.
5. the oral formulations of claim 1, edible oil wherein is a vegetable oil.
6. the oral formulations of claim 5, vegetable oil wherein is selected from American Avocado Tree oil, olive oil and Flos Carthami oil.
7. the oral formulations of claim 1, suspension wherein is encapsulated in the controlled release coat.
8. the oral formulations of claim 7, controlled release coat wherein is used for discharging at small intestinal.
9. the oral formulations of claim 7, controlled release coat wherein is used for discharging at large intestine.
10. the oral formulations of claim 7, controlled release coat wherein is used for discharging under one's belt.
11. comprising to the mammal oral administration, the method for treatment mammal gastrointestinal inflammation, this method contain the suspension of effective dose budesonide in edible oil.
12. the method for claim 11, wherein, with at least 4 weeks of suspension administration every day.
13. the method for claim 11, mammal wherein are the initial dose administrations with the 0.1mg/kg budesonide of Canis familiaris L. and every day.
14. the method for claim 11, mammal wherein are the initial dose administrations with the 0.4mg/kg budesonide of cat and every day.
15. the method for claim 11, mammal wherein are the initial dose administrations with the 0.1mg/kg budesonide of people and every day.
16. the method for claim 11 wherein, with the initial dose twice about 2-4 of administration week of every day, alleviates minimizing dosage according to symptom subsequently.
17. the method for claim 16 wherein, reduces dosage with about 1/3 to 1/2 of initial dose subsequently.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1998/002265 WO1999039699A1 (en) | 1998-02-09 | 1998-02-09 | Treatment of chronic inflammatory disorders of the gastrointestinal tract |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1284869A true CN1284869A (en) | 2001-02-21 |
| CN1149078C CN1149078C (en) | 2004-05-12 |
Family
ID=22266344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB988135329A Expired - Fee Related CN1149078C (en) | 1998-02-09 | 1998-02-09 | Treatment of chronic inflammatory disorders of gastrointestinal tract |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1052977A4 (en) |
| JP (1) | JP2002502812A (en) |
| KR (1) | KR20010040646A (en) |
| CN (1) | CN1149078C (en) |
| AU (1) | AU735084B2 (en) |
| CA (1) | CA2320087C (en) |
| IL (1) | IL137598A (en) |
| SE (1) | SE0002831L (en) |
| WO (1) | WO1999039699A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100333727C (en) * | 2004-11-25 | 2007-08-29 | 天津药业研究院有限公司 | Budesonide target-direction microball and preparation thereof |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD2852C2 (en) * | 2005-03-28 | 2006-04-30 | Георге АНГЕЛИЧ | Use of budesonide for treatment of resistant ascites to pacients with hepatic cirrhosis |
| 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 |
| CA2677842C (en) * | 2007-02-16 | 2014-09-16 | Aska Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising microparticle oily suspension |
| US8865692B2 (en) | 2007-11-13 | 2014-10-21 | Meritage Pharma, Inc | Compositions for the treatment of gastrointestinal inflammation |
| DK2214679T3 (en) | 2007-11-13 | 2019-05-20 | Meritage Pharma Inc | CORTICOSTEROID COMPOSITIONS |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5643602A (en) * | 1989-11-22 | 1997-07-01 | Astra Aktiebolag | Oral composition for the treatment of inflammatory bowel disease |
| SK282826B6 (en) * | 1991-12-18 | 2002-12-03 | Aktiebolaget Astra | New combination of formoterol and budesonide |
| 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 |
| US6214378B1 (en) * | 1996-08-02 | 2001-04-10 | Hisamitsu Pharmaceutical Co., Inc. | Capsules for oral preparations and capsule preparations for oral administration |
| KR100219918B1 (en) * | 1997-07-03 | 1999-09-01 | 김윤 | Composition for colon specific drug delivery |
-
1998
- 1998-02-09 KR KR1020007008518A patent/KR20010040646A/en not_active Application Discontinuation
- 1998-02-09 WO PCT/US1998/002265 patent/WO1999039699A1/en not_active Application Discontinuation
- 1998-02-09 EP EP98907382A patent/EP1052977A4/en not_active Withdrawn
- 1998-02-09 AU AU63200/98A patent/AU735084B2/en not_active Ceased
- 1998-02-09 JP JP2000530199A patent/JP2002502812A/en active Pending
- 1998-02-09 IL IL13759898A patent/IL137598A/en not_active IP Right Cessation
- 1998-02-09 CN CNB988135329A patent/CN1149078C/en not_active Expired - Fee Related
- 1998-02-09 CA CA002320087A patent/CA2320087C/en not_active Expired - Fee Related
-
2000
- 2000-08-07 SE SE0002831A patent/SE0002831L/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100333727C (en) * | 2004-11-25 | 2007-08-29 | 天津药业研究院有限公司 | Budesonide target-direction microball and preparation thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1052977A4 (en) | 2006-07-12 |
| WO1999039699A1 (en) | 1999-08-12 |
| CN1149078C (en) | 2004-05-12 |
| AU6320098A (en) | 1999-08-23 |
| EP1052977A1 (en) | 2000-11-22 |
| SE0002831L (en) | 2000-09-28 |
| CA2320087C (en) | 2006-12-19 |
| SE0002831D0 (en) | 2000-08-07 |
| KR20010040646A (en) | 2001-05-15 |
| IL137598A (en) | 2005-09-25 |
| IL137598A0 (en) | 2001-07-24 |
| AU735084B2 (en) | 2001-06-28 |
| JP2002502812A (en) | 2002-01-29 |
| CA2320087A1 (en) | 1999-08-12 |
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