WO2005073220A1 - 下痢型過敏性腸症候群治療剤 - Google Patents
下痢型過敏性腸症候群治療剤 Download PDFInfo
- Publication number
- WO2005073220A1 WO2005073220A1 PCT/JP2004/006657 JP2004006657W WO2005073220A1 WO 2005073220 A1 WO2005073220 A1 WO 2005073220A1 JP 2004006657 W JP2004006657 W JP 2004006657W WO 2005073220 A1 WO2005073220 A1 WO 2005073220A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- parts
- acid
- ramosetron
- bowel syndrome
- irritable bowel
- Prior art date
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Classifications
-
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- 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
Definitions
- the present invention relates to a medicament, in particular, an agent for treating diarrhea-type irritable bowel syndrome or an agent for improving diarrheal symptoms of irritable bowel syndrome.
- Ramosetron has the chemical name (1) -1 (R) -5-[(1-methyl-1H-Indone-l-3-yl) caprolponyl] -4,5,6,7-tetrahydro-1H-benzimidazole Name.
- Ramosetron hydrochloride is marketed as a drug to improve gastrointestinal symptoms (nausea, vomiting) associated with the administration of antineoplastic drugs (cisbratine, etc.).
- antineoplastic drugs cisbratine, etc.
- the EP-A-381422 it is disclosed that a series of tetrahydro base Nzuimidazoru derivatives including ramosetron and pharmaceutically acceptable salts has 5 HT 3 receptor antagonism. Based on this effect, it suggests the possibility of preventing and treating vomiting caused by anticancer drugs such as cisplatin and radiation, migraine, combined headache, trigeminal neuralgia, anxiety, dyskinesia, peptic ulcer, irritable bowel syndrome, etc.
- the clinical dose is usually 0.1 to 10 mg IV for adults and 0.5 to 50 mg orally per day, and it is described that these may be administered once or divided into several doses. .
- the W099 / 17755, 5 HT 3 receptor antagonists have been described to be useful in the treatment of non-constipation type irritable bowel syndrome patients women, a therapeutically effective amount of one day 0. 01 ⁇ 500Mg Example
- the box indicates that it is preferably 0.05 to 50 mg.
- arosetron l to 8 mg was administered twice daily to patients with non-constipated irritable bowel syndrome, female patients had less pain and discomfort than placebo, and It was noted that there was a significant improvement in the frequency of defecation and the proportion of days requiring urgency, but no significant improvement was seen in male patients over placebo except for stool consistency.
- the W0200V007713, 5 HT 3 receptor antagonist 3 times a day are described to be useful in the treatment of irritable bowel syndrome in men and women by Azukasuru projecting the L ⁇ 16mg. Disclosure of the invention
- the present inventors have conducted intensive studies for the purpose of creating a novel therapeutic drug for diarrhea-type irritable bowel syndrome without a sufficiently effective therapeutic drug.
- the present inventors have previously attempted a clinical test in which ramosetron hydrochloride was administered twice a day to a patient with irritable bowel syndrome, but could not confirm a significant therapeutic effect on placebo.
- the present inventors have found that the therapeutically effective amount of ramosetron hydrochloride for irritable bowel syndrome can be adjusted to the dose currently used as an agent for improving gastrointestinal symptoms induced by administration of an anti-neoplastic agent from 0.1 to 0. I was inspired to see a dose much lower than 3 mg. Therefore, a stable formulation containing a very low dose (0.001 to 0.01 mg) of ramosetron hydrochloride was developed, and using such a formulation, it was possible to treat male and female patients with diarrhea-sensitive irritable bowel syndrome in 12 weeks. Extensive clinical trials have shown surprisingly remarkable efficacy and completed the invention.
- the present invention provides a daily dose of 0.002-0.02 mg of ramosetron hydrochloride or an equimolar amount of ramosetron or a pharmaceutically acceptable amount thereof for the manufacture of a therapeutic agent for diarrhea irritable bowel syndrome in male and female patients. Or other salts, or as a daily dose for the manufacture of diarrhea ameliorating agents for irritable bowel syndrome in men and women
- the present invention relates to the use of 0.002 to 0.02 mg of ramosetron hydrochloride or an equimolar amount of ramosetron or other pharmaceutically acceptable salts.
- an excellent therapeutic agent for diarrhea-type irritable bowel syndrome effective regardless of gender Can provide an agent for improving irritable bowel syndrome diarrhea.
- Test Example 1 ramosetron hydrochloride was effective for male and female patients with diarrhea-sensitive irritable bowel syndrome by oral administration of 0.005 mg or O. Olmg once daily.
- O.OOSmg administration resulted in a remarkable therapeutic effect that was not different from O.Olmg administration. Therefore, efficacy can be expected even with about half this amount.
- the subjects of Test Example 2 are Japanese adult patients, suggesting that the optimal dose for children may be even smaller, while the optimal dose for Europeans and Americans is twice as large as that for Japanese patients. It is common.
- the particularly preferred dose of ramosetron hydrochloride is in the range of 0.002 to 0.02 mg per day, but the daily dose is in the range of 0.001 to 0.05 rag depending on the age and ethnicity of the patient. It is considered that irritable bowel syndrome or irritable bowel syndrome can improve diarrhea symptoms.
- EP-A-381422 states that the clinical dose of a tetrahydrobenzimidazole derivative containing ramosetron is usually 0.1 mg or more per day, and that the daily dose of ramosetron hydrochloride is 0.002 to 0. There is no indication or disclosure of a therapeutic effect in the range of 02 mg.
- the present invention provides 1) a therapeutically effective amount of 1/5 to 1 / l of a currently marketed ramosetron hydrochloride as an active ingredient for an agent for improving digestive organ symptoms induced by administration of an anti-neoplastic agent. 3) 02002/007713 for the drug disclosed in TO99 / 17755, in that it provides a sufficient therapeutic effect for both male and female patients.
- the drugs disclosed in the above are each excellent in that a sufficient therapeutic effect can be obtained by once-daily administration of a very low dose of 1/50 to 1/500. It is unpredictable.
- the present invention will be described in more detail.
- Ramosetron and its pharmaceutically acceptable salts can be easily obtained by the method described in EP-A-381422 or according to it.
- ramosetron examples include, for example, mineral salts with hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, etc., acetic acid, oxalic acid, succinic acid, citric acid, maleic acid And salts with organic acids such as malic acid, fumaric acid, tartaric acid and methanesulfonic acid, and salts with acidic amino such as glutamic acid and aspartic acid.
- Commercially available ramosetron hydrochloride is preferred.
- the drug of the present invention is prepared as an oral solid preparation, an oral liquid preparation or an injection using an organic or inorganic carrier, excipient, or other additive suitable for oral or parenteral administration according to a conventional method. be able to.
- oral solid preparations that can be easily taken by the patient themselves and are easy to store and carry. Specific examples include tablets, powders, granules, fine granules, capsules, and pills.
- the active substance is mixed with at least one inert diluent, for example, lactose, mannitol, glucose, microcrystalline cellulose, starch, polyvinylpyrrolidone, magnesium aluminate metasilicate.
- the composition may be prepared according to conventional methods using additives other than inert diluents, for example, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, magnesium stearate, calcium stearate, polyethylene glycol, starch, and talc.
- tablets or pills may be coated with sugar coating such as sucrose, gelatin, agar, pectin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate or a film of a gastric or enteric substance.
- a plasticizer such as carboxylic acid 80, triacetin, and a coloring agent such as titanium oxide and iron sesquioxide.
- tablets or pills may be coated with sugar coating such as sucrose, gelatin, agar, pectin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate or a film of a gastric or enteric substance.
- Orally disintegrating tablets such as commercially available “Nazea D tablets 0.1 mg” may be used.
- an orally disintegrating tablet can be prepared according to US 5,466, 464, US 5, 576, 014, US 6, 589, 554, W02003 / 00983K TO2002 / 092057, and the like.
- the medicament of the present invention contains a very low dose of ramosetron, a preparation provided with a technology for stabilizing against temperature and humidity is particularly preferable.
- a specific compound having a carbonyl group for example, by adding a specific compound having a carbonyl group, stabilization of ramosetron against temperature and humidity can be achieved.
- Specific examples of the specific compound having a carbonyl group include aliphatic carboxylic acids (specifically, saturated or unsaturated, linear or branched aliphatic mono-, di- or tricarboxylic acids.
- Aliphatic carboxylic acids having 3 to 36 carbon atoms or esters thereof Aliphatic carboxylic acids having 3 to 36 carbon atoms or esters thereof, hydroxycarboxylic acids (specifically, saturated or unsaturated, linear or branched aliphatic hydroxy monols, di- or tricarboxylic acids) In particular, hydroxycarboxylic acids having 3 to 36 carbon atoms) or esters thereof, acidic amino acids, enolic acid, and aromatic carboxyl compounds (specifically, alkyl groups having 1 to 4 carbon atoms, substituted by hydroxy groups) Aromatic mono-, di- or tricarboxylic acids which may be used, in particular, aromatic carboxylic acids having 7 to 20 carbon atoms) or esters thereof, and high molecular weight compounds having a carbonyl group; Can be used alone or in combination of two or more.
- hydroxycarboxylic acids specifically, saturated or unsaturated, linear or branched aliphatic hydroxy monols, di- or tricar
- a polymer having a carboxylic acid group, an aromatic carboxyl compound or an ester thereof, and a hydroxylic acid are preferable.
- a polymer having an acid or an ester thereof, a carboxylic acid group or an aromatic carboxyl compound or an ester thereof is preferred, and a hydroxycarboxylic acid or an ester thereof or a polymer having a carboxyl group is more preferred.
- Preferred aliphatic carboxylic acids are maleic acid, malonic acid, succinic acid, and fumaric acid.
- the hydroxycarboxylic acid is preferably tartaric acid, malic acid or citric acid, and more preferably tartaric acid or citric acid.
- Preferred as an acidic amino acid is diaspartic acid glutamate.
- the aromatic propyloxyl compound is preferably phthalic acid or propyl gallate, and more preferably propyl gallate.
- the high molecular substance having a carboxyl group is hydroxypropylmethylcellulose or alginic acid, and more preferably, carboxymethylcellulose.
- enolic acid preferred are ascorbic acid and erythorbic acid, and more preferred is ascorbic acid.
- hydrates and anhydrides having no water of crystallization such as hydrated hydrate or hydrated anhydride
- hydrates, anhydrides, and mixtures thereof are not particularly limited.
- the weight average molecular weight is about 110,000, and for alginic acid, it is about 200,000.
- the amount of the compound that stabilizes ramosetron or a pharmaceutically acceptable salt thereof is not particularly limited as long as it achieves the stabilization.
- the content is 0.01 to 90% by weight, preferably 0.01 to 50% by weight, and more preferably 0.1 to 10% by weight in consideration of manufacturability.
- the dose of ramosetron or a pharmaceutically acceptable salt thereof is appropriately determined depending on the individual case in consideration of the administration route, the symptoms of the disease, the age, race, sex, etc. of the administration subject.
- Oral administration of ramosetron hydrochloride is usually about 0.001 to 0.05 mg / day for an adult, most preferably 0.002 to 0.02 mg / day, once daily after meals. Administer.
- Example 2 FLOW C0ATER, manufactured by Freund) and spraying the spray liquid at a spray rate of 5 g / min. The fluidized granulation was performed. After the granulation, the granulated product was dried at an intake air temperature of 40 ° C. for 5 minutes, and then 0.3 parts of light anhydrous silicic acid was mixed to obtain a powder.
- Example 2
- the mixed powder was tableted at 120 mg / tablet using a rotary tableting machine to give tablets having an initial hardness of about lkp. This was stored at 25 ° C and a relative humidity of 75% for 18 hours, and then stored at 30 and a relative humidity of 40% for 4 hours to obtain an orally disintegrating tablet.
- Example 3
- Example 4 An orally disintegrating tablet was obtained in the same production method as in Example 2 except that the amount of citrate anhydride was changed to 0.2 part.
- Example 4 An orally disintegrating tablet was obtained in the same production method as in Example 2 except that the amount of citrate anhydride was changed to 0.2 part.
- the mixed powder was tableted at 120 mg per tablet using a rotary tableting machine to give tablets having an initial hardness of about lkp. This was stored at 25 ° C and a relative humidity of 75 for 18 hours, and then stored at 30 ° C and a relative humidity of 40 for 4 hours to obtain an orally disintegrating tablet.
- Example 6
- a tablet was prepared in the same manner as in Example 5 except that the amount of ascorbic acid was changed to 0.5 part, to give an orally disintegrating tablet.
- Example 7
- Magnesium stearate 1 part 10 parts of maltose, 0.0008 part of ramosetron hydrochloride, 1 part of red iron sesquioxide and 0.2 part of citric anhydride were stirred and suspended in 67 parts of water using a magnetic stirrer to obtain a spray liquid (concentration: 15 wt. %) Was prepared.
- 88 parts of mannitol were charged into a fluidized bed granulator (FLOW C0ATER, manufactured by Freund), and the intake temperature was 50 ° (: spray rate 10 gZmin, spray Z dry Z shaking cycle 15 seconds / 15 seconds.
- the above-mentioned spray liquid was sprayed to perform fluid granulation.
- the granulated product was dried at an intake air temperature of 40 ° C. for 5 minutes, and 1 part of magnesium stearate was mixed.
- the mixed powder was broken at 120 mg / tablet using a tablet / tablet / tablet machine to obtain a tablet having an initial hardness of about lkp, which was stored at 25 ° C and a relative humidity of 75% for 18 hours.
- the tablets were stored at 30 ° C and a relative humidity of 40% for 4 hours to obtain orally disintegrating tablets.
- the granulated product was dried at an intake air temperature of 40 ° C for 5 minutes, and then 0.5 part of magnesium stearate was mixed.
- the mixed powder was tableted at 100 mg / tablet using a Rosewood tableting machine to obtain tablets.
- Investigational drug and administration method placebo, ramosetron hydrochloride 0.005 mg or O.Oimg once daily ⁇ weekly oral administration
- Study period 1 week observation period, 12 weeks treatment period
- the subjects After the transition to the treatment period, with the first day of taking the study drug as the first day, the subjects compared all the symptoms of IBS every ⁇ weeks and compared the overall improvement effect of the study drug with respect to the IBS symptoms in the observation period. And completed the patient diary.
- the scores for the overall improvement of IBS symptoms were as follows.
- Monthly responder rates were calculated for each of the placebo, ramosetron hydrochloride 0.005 mg, and O. Olmg groups, using subjects who scored 0 or 1 for more than 2 weeks out of 4 weeks as monthly responders. .
- the subjects After the transition to the treatment period, on the first day of taking the investigational drug, the subjects evaluated the abdominal pain and abdominal discomfort improvement effect of the investigational drug every week by comparing it with the state during the observation period, and entered in the patient diary.
- the evaluation scores for the effect of improving abdominal pain and abdominal discomfort were as follows.
- the subjects After the transition to the treatment period, starting on the first day of taking the investigational drug, the subjects evaluated the effect of the investigational drug on the improvement of bowel movements every week by comparing it with the state during the observation period, and entered in the patient diary.
- subjects recorded their daily stool shape (properties) in the patient diary using the Bristol stool shape scale score (type).
- type Bristol stool shape scale score
- the subject's stool of the most typical (felt most annoying) stool of the day was taken. Only one shape (properties) was entered.
- the final month responder rates for the effects of improving abdominal pain / abdominal discomfort and improving bowel movement were more than 10% higher in the ramosetron hydrochloride 0.005 mg and 0.1 Olmg groups than in the brasepo group.
- an excellent therapeutic agent for diarrhea-type irritable bowel syndrome or an agent for improving diarrheal symptom of irritable bowel syndrome, which is effective regardless of gender, can be provided.
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Abstract
Description
Claims
Priority Applications (18)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/JP2004/006657 WO2005073220A1 (ja) | 2004-01-30 | 2004-05-12 | 下痢型過敏性腸症候群治療剤 |
RU2005127333/15A RU2314808C2 (ru) | 2004-01-30 | 2005-01-27 | Средство для лечения синдрома раздраженного кишечника с преобладанием диареи |
MXPA05009025A MXPA05009025A (es) | 2004-01-30 | 2005-01-27 | Agentes de tratamiento para el sindrome de intestino delgado irritado con diarrea predominante. |
BRPI0503488-4A BRPI0503488A (pt) | 2004-01-30 | 2005-01-27 | agente de tratamento para sìndrome de intestino irritável com diarréia predominante |
CNB2005800000636A CN100372533C (zh) | 2004-01-30 | 2005-01-27 | 腹泻为主大肠激惹综合征的治疗制剂 |
AU2005209112A AU2005209112B2 (en) | 2004-01-30 | 2005-01-27 | Therapeutic agent for diarrhea-type irritable bowel syndrome |
PL380448A PL380448A1 (pl) | 2004-01-30 | 2005-01-27 | Środek do leczenia dominującego zespołu drażliwego jelita grubego typu biegunkowego |
CA002516433A CA2516433C (en) | 2004-01-30 | 2005-01-27 | Ramosetron hydrochloride for diarrhea-predominant irritable bowel syndrome |
NZ541656A NZ541656A (en) | 2004-01-30 | 2005-01-27 | The use of ramosetron hydrochloride for diarrhea-predominant irritable bowel syndrome |
KR1020057016208A KR100746444B1 (ko) | 2004-01-30 | 2005-01-27 | 설사-우세형 과민성 대장 증후군의 치료제 |
PCT/JP2005/001549 WO2005072730A1 (ja) | 2004-01-30 | 2005-01-27 | 下痢型過敏性腸症候群治療剤 |
US11/047,142 US7358270B2 (en) | 2004-01-30 | 2005-01-28 | Treating agent for irritable bowel syndrome |
AT05001928T ATE516061T1 (de) | 2004-01-30 | 2005-01-31 | Medikament zur behandlung des reizdarmsyndroms mit diarrhö |
EP05001928A EP1559446B1 (en) | 2004-01-30 | 2005-01-31 | Treating agent for diarrhea-predominant irritable bowel syndrome |
NO20054002A NO20054002L (no) | 2004-01-30 | 2005-08-29 | Behandlingsmiddel for diar±-predominant irritabel tarmsyndrom |
US11/583,234 US7683090B2 (en) | 2004-01-30 | 2006-10-18 | Treating agent for irritable bowel syndrome |
HK06111414A HK1090561A1 (en) | 2004-01-30 | 2006-10-18 | Therapeutic agent for diarrhea-type irritable bowel syndrome |
RU2007119067/15A RU2351327C2 (ru) | 2004-01-30 | 2007-05-22 | Средство для лечения синдрома раздраженного кишечника с преобладанием диареи |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/JP2004/000896 WO2004066998A1 (ja) | 2003-01-31 | 2004-01-30 | 安定な経口用固形医薬組成物 |
JPPCT/JP2004/000896 | 2004-01-30 | ||
PCT/JP2004/006657 WO2005073220A1 (ja) | 2004-01-30 | 2004-05-12 | 下痢型過敏性腸症候群治療剤 |
PCT/JP2005/001549 WO2005072730A1 (ja) | 2004-01-30 | 2005-01-27 | 下痢型過敏性腸症候群治療剤 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2004/000896 Continuation-In-Part WO2004066998A1 (ja) | 2003-01-31 | 2004-01-30 | 安定な経口用固形医薬組成物 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/047,142 Continuation-In-Part US7358270B2 (en) | 2004-01-30 | 2005-01-28 | Treating agent for irritable bowel syndrome |
Publications (1)
Publication Number | Publication Date |
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WO2005073220A1 true WO2005073220A1 (ja) | 2005-08-11 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/JP2004/006657 WO2005073220A1 (ja) | 2004-01-30 | 2004-05-12 | 下痢型過敏性腸症候群治療剤 |
Country Status (1)
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WO (1) | WO2005073220A1 (ja) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001518495A (ja) * | 1997-10-07 | 2001-10-16 | グラクソ グループ リミテッド | 薬 剤 |
WO2002007713A2 (de) * | 2000-07-26 | 2002-01-31 | Solvay Pharmaceuticals Gmbh | Cilansetron enthaltende arzneimittel zur behandlung nicht-obstipativer männlicher ibs-patienten |
US20030143548A1 (en) * | 2002-01-28 | 2003-07-31 | Camilleri Michael L. | Predicting patient responsiveness to serotonergic therapy |
-
2004
- 2004-05-12 WO PCT/JP2004/006657 patent/WO2005073220A1/ja active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001518495A (ja) * | 1997-10-07 | 2001-10-16 | グラクソ グループ リミテッド | 薬 剤 |
WO2002007713A2 (de) * | 2000-07-26 | 2002-01-31 | Solvay Pharmaceuticals Gmbh | Cilansetron enthaltende arzneimittel zur behandlung nicht-obstipativer männlicher ibs-patienten |
US20030143548A1 (en) * | 2002-01-28 | 2003-07-31 | Camilleri Michael L. | Predicting patient responsiveness to serotonergic therapy |
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