AP544A - Compositions for rectal administration - Google Patents
Compositions for rectal administration Download PDFInfo
- Publication number
- AP544A AP544A APAP/P/1994/000643A AP9400643A AP544A AP 544 A AP544 A AP 544A AP 9400643 A AP9400643 A AP 9400643A AP 544 A AP544 A AP 544A
- Authority
- AP
- ARIPO
- Prior art keywords
- methyl
- suppository
- active ingredient
- rectal administration
- pharmaceutically acceptable
- Prior art date
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
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- 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
- A61K31/415—1,2-Diazoles
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a pharmaceutical composition for rectal administration
Description
COMPOSITIONS FOR RECTAL ADMINISTRATION
The present invention relates to a pharmaceutical composition containing, as active ingredient, 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1 -yl)methyl]-4H-carbazol-4-one, in particular a composition for rectal administration.
1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1 -yl)-methyl]-4H-carbazol4-one, which may be represented by the formula (I)
and its physiologically acceptable salts and solvates are disclosed in GB2153821. The compound of formula (I) is described as a potent and selective antagonist of 5-hydroxytryptamine (5-HT) at neuronal 5-HT receptors of the type located on terminals of primary afferent nerves. Receptors of this type are now designated as 5-HT3 receptors and are also present in the central nervous system. 5-HT occurs widely in the neuronal pathways in the central nervous system and disturbance of these 5-HT containing pathways is known to alter behavioural syndromes such as mood, psychomotor activity, appetite and memory.
The compound is described as being of use in the treatment of a human or animal subject suffering from a condition caused by a disturbance of neuronal 5HT function, for example in the treatment of a human subject suffering from migraine pain or a psychotic disorder such as schizophrenia. It is also stated that the compound may be useful in the treatment of conditions such as anxiety, obesity and mania.
bad original $
AP. Ο Ο 5 4 4
-2Subsequently published patent applications disclose the use of the compound of formula (I) and other 5-HT3 antagonists for the treatment of a number of other conditions such as dementia, cognitive disorders and emesis.
Numerous clinical studies have demonstrated the effectiveness of the 5 compound of formula (I) for the treatment of emesis, particularly the nausea and vomiting associated with cancer chemotherapy and radiotherapy and that occurring post-operatively. Hitherto, the drug has always been administered in the form of a salt, in particular in the form of its hydrochloride dihydrate salt, either by injection or orally.
Oral administration constitutes the generally preferred route for administration of pharmaceuticals since this route is particularly convenient and acceptable to patients. Unfortunately oral compositions may be associated with certain disadvantages, particularly in the treatment of conditions accompanied by nausea and/or vomiting. It is highly desirable, particularly in the treatment of acute conditions, that pharmaceutical compositions have a rapid and consistent onset of action combined with sustained activity and good bioavailability. Rapid absorption can be achieved by parenteral injection but this is unacceptable to some patients, particularly if the drug is to be administered without direct medical supervision i.e. self-administered.
Alternative routes for administration of the compound of formula (I) are proposed in GB 2153821 including rectal administration. GB 2153821 specifically discloses a number of pharmaceutical formulations containing
1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1 -yl)-methyl]-4H-carbazol4-one hydrochloride dihydrate as active ingredient and a specific suppository formulation for rectal administration containing this active ingredient has been disclosed in, for example, EP-0278161.
The present invention provides a particularly advantageous pharmaceutical formulation, not hitherto specifically disclosed, which is suitable for rectal administration of the compound of formula (I).
AP/P/ 93/00645 bad original
There is thus provided according to the invention a pharmaceutical composition for rectal administration which comprises 1,2,3,9-tetrahydro-9-methyl-3-[(2methyl-1H-imidazol-1-yl)-methyl]-4H-carbazol-4-one in the form of its free base or a pharmaceutically acceptable solvate thereof as active ingredient, together with one or more pharmaceutically acceptable carriers or excipients.
Unlike the prior art compositions, the compositions according to the invention contain the active ingredient in the form of its free base or a pharmaceutically acceptable solvate thereof. The applicants have found that the use of the free base rather than the hydrochloride salt of the compound of formula (I) is surprisingly advantageous when the active ingredient is administered rectally.
The compositions according to the invention may be in the form of retention enemas, solid dosage forms such as suppositories or soft gelatin capsules, or semi solid dosage forms such as a rectal gel or cream. Preferably the p-j compositions are formulated as solid unit dosage forms suitably shaped, for example conical, cylindrical or torpedo-shaped, for rectal administration. The solid dosage forms may either melt at body temperature or dissolve or disperse in the mucous secretions of the cavity.
Conventional carriers which may be employed in the compositions according to the invention include theobroma oil, hard fats, glycerides of fatty acids, glycerol20 gelatin bases, macrogols (polyethylene glycols) and mixtures thereof. Preferred compositions comprise hard fat bases such as esterified, hydrogenated or fractionated vegetable oils and synthetic triglyceride mixtures produced under the name of adeps solidus.
Preferred hard fat bases are hard fats containing a mixture of mono-, di- and triglycerides of saturated Cg-ig fatty acids. Preferably the hard fat base comprises hard fats obtained by esterification of fatty acids of vegetable origin with glycerol, a macrogol ether containing 20 to 24 oxyethylene groups in the polyoxyethylene chain e.g. polyoxyl-20-cetostearyl ether, and glycerides e.g. glyceryl ricinoleate. Preferably the hard fat base has a high Hydroxyl Value
BAD ORIGINAL $
AP.00544
- 4 (USP Chemical Test), for example a Hydroxyl Value of between 20 and 100, such as 40 to 80, in particular 60 to 70.
Solid dosage forms such as suppositories may be prepared in conventional manner for example by intimate admixture of the active ingredient with the carrier, preferably the molten carrier. Preferably the active ingredient is milled or sieved prior to incorporation into the molten carrier. The molten composition may then be poured into suitable moulds, for example PVC, polyethylene or aluminium moulds. Optionally the suppositories may be coated, prior to packing, for example with cetyl alcohol, macrogol or polyvinyl alcohol and polysorbates to increase disintegration time or lubrication or to reduce adhesion on storage.
Preferably the total weight of the solid dosage form is about 1 or 2 grams and the active ingredient may comprise 0.05 to 20% by weight of the compositon, preferably 0.1 to 20% by weight of the composition, more preferably 0.2 to 5% by weight of the composition, such as 0.4 to 3.2%.
The amount of 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1 -yl)methyl]-4H-carbazol-4-one free base employed in the compositions of the invention will preferably be in the range of about 0.1 mg to about 100mg, more preferably about 1mg to about 50mg, such as about 2mg to about 35mg, for example about 5mg to about 20mg.
A further aspect of the invention provides a method of treating a mammal, including man, suffering from or susceptible to a condition mediated through the action of 5-hydroxytryptamine at 5-HT3 receptors which comprises rectal administration of a pharmaceutical composition which comprises 1,2,3,925 tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1 -yl)-methyl]-4H-carbazol-4-one in the form of its free base or a pharmaceutically acceptable solvate thereof as active ingredient, together with one or more pharmaceutically acceptable carriers or excipients. It will be appreciated that reference to treatment is
AP/P/ 93/00645
BAD ORIGINAL $
- 5 intended to include prophylaxis as well as the alleviation of established symptoms.
Conditions mediated through the action of 5-HT at 5-HT3 receptors include cognitive disorders such as dementia, particularly degenerative dementia (including senile dementia, Alzheimer's disease, Pick's disease, Huntington's chorea, Parkinson’s disease and Creutzteldt-Jakob disease), and vascular dementia (including multi-infarct dementia), as well as dementia associated with intracranial space occupying lesions, trauma, infections and related conditions (including HIV infection), metabolism, toxins, anoxia and vitamin deficiency; and mild cognitive impairment associated with ageing, particularly Age Associated Memory Impairment; psychotic disorders, such as schizophrenia and mania; anxiety disorders, including panic disorder, agoraphobia, social phobia, simple phobia, obsessive compulsive disorders, post traumatic stress disorder, mixed anxiety and depression, and generalised anxiety disorder; nausea and vomiting, particularly that associated with cancer chemotherapy and radiotherapy and also that occurring post operatively; irritable bowel syndrome and dependency on drugs and substances of abuse. Other conditions mediated in this manner include gastric stasis; symptoms of gastrointestinal dysfunction such as occur with peptic ulcer, reflux oesophagitis, flatulence and dyspepsia; migraine; obesity and conditions such as bulimia; pain; and depression.
The pharmaceutical compositions according to the invention have particular utility for the treatment of nausea and vomiting, particularly that associated with cancer chemotherapy and radiotherapy, but also that occurring post-operatively.
It will be appreciated that the precise therapeutic dose of the active ingredient 25 will depend on the age and condition of the patient and the nature of the condition to be treated and will be at the ultimate discretion of the attendant physician.
However, in general, effective doses for the treatment of conditions mediated through the action of 5-hydroxytryptamine at 5-HT3 receptors, for example post-
BAD ORIGINAL $
AP.00544
-6 operative nausea and vomiting will lie in the range of 0.1 to 200mg, preferably
0.5 to 100mg, most preferably 1 to 50mg, for example 4, 8, 16 or 32mg of the active ingredient per unit dose which could be administered in single or divided doses, for example, 1 to 4 times per day.
The invention is further illustrated by the following non-limiting examples.
Example. 1
Suppository for Rectal Administration Unit Formula (per suppository)
1,2,3,9-Tetrahydro-9-methyl-3-[(2-methyl-1 Himidazol-1 -yl)-methyl]-4H-carbazol-4-one 8mg (sieved free base)
Mixture of hard fats NF17, polyoxy-20-cetostearyl- to 1g ether NF17 and glyceryl ricinoleate (sold under the trade name Witepsol S58)
Hydroxyl Value 60 to 70
A suspension of the active ingredient in molten base was prepared and filled in conventional manner into 1g size suppository moulds.
Examples 2. 3. 4 and 5
Suppositories containing 1, 2, 4 or 16mg 1,2,3,9-tetrahydro-9-methyl-3-[(2methyl-1 H-imidazol-1-yl)-methyl]-4H-carbazol-4-one (sieved free base) were prepared as described for the suppositories of Example 1.
AP/P/ 93/0064 5
Example^
Suppository for Rectal Administration
Unit Formula (per suppository)
1,2,3,9-Tetrahydro-9-methyl-3-[(2-methyl-1 Himidazol-1-yl)-methyl]-4H-carbazol-4-one · 16mg (sieved free base)
Mixture of hard fats NF17, polyoxy-20-cetostearyl- to 2g : ether NF17 and glyceryl ricinoleate (sold under the trade name Witepsol S58)
Hydroxyl Value 60 to 70
A suspension of the active ingredient in molten base was prepared and filled in conventional manner into 2g size suppository moulds.
Examples 7 and 8
Suppositories containing 8 or 32mg 1,2,3,9-tetrahydro-9-methyl-3'[(2-methyl1H-imidazol-1-yl)-methyl]-4H-carbazol-4-one (sieved free base) were prepared as described for the suppositories of Example 6,
Example 9
Suppositories containing 4mg 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H10 imidazol-1-yl)-methyl]-4H-carbazol-4-one (sieved free base) are prepared as described for the suppositories of Example 6.
Claims (7)
- Claims1. A suppository for rectal administration which comprises 1,2,3,9-tetrahydro9-methyl-3-[(2-rnethyl-1H-imidazol-1-yl)-methyl]-4H-carbazol-4-one in the form of its free base or a pharmaceutically acceptable solvate thereof as active5 ingredient, together with one or more pharmaceutically acceptable carriers or excipients.
- 2. A suppository as claimed in claim 1 wherein the pharmaceutical carrier comprises hard fat bases.
- 3. A suppository as claimed in claim 2 wherein the hard fat base has a 10 Hydroxyl Value of between 20 to 100.
- 4. A suppository as claimed in any of claims 1 to 3 which comprises 0.05 to 20% by weight of active ingredient.
- 5. A suppository as claimed in any one of claims 1 to 4 which comprises 0.1 to 100mg of active ingredient.ZPZ 9 4 / 0 &
- 6 4 315 6. A method of manufacture of a suppository as claimed in any one of claims1 to 5 which comprises intimate admixture of the active ingredient with the carrier.
- 7. A method of treating a mammal, including man, suffering from or susceptible to a condition mediated through the action of 5-hydroxytryptamine at20 5-HT3 receptors which comprises rectal administration of a suppository which comprises 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1-yl)-methyl]4H-carbazol-4-one in the form of its free base or a pharmaceutically acceptable solvate thereof as active ingredient, together with one or more pharmaceutically acceptable carriers or excipients.BAD ORIGINAL1122SN-98. A method according to claim 7 wherein the condition is nausea and vomiting.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB939310756A GB9310756D0 (en) | 1993-05-25 | 1993-05-25 | Compositions |
Publications (2)
Publication Number | Publication Date |
---|---|
AP9400643A0 AP9400643A0 (en) | 1994-07-31 |
AP544A true AP544A (en) | 1996-10-11 |
Family
ID=10736089
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
APAP/P/1994/000643A AP544A (en) | 1993-05-25 | 1994-05-23 | Compositions for rectal administration |
Country Status (38)
Country | Link |
---|---|
US (1) | US5741806A (en) |
EP (1) | EP0700290B1 (en) |
JP (1) | JP2965703B2 (en) |
KR (1) | KR100297212B1 (en) |
CN (1) | CN1106194C (en) |
AP (1) | AP544A (en) |
AT (1) | ATE183643T1 (en) |
AU (1) | AU680918B2 (en) |
BE (1) | BE1007158A3 (en) |
BR (1) | BR1100046A (en) |
CA (1) | CA2162919C (en) |
CO (1) | CO4230094A1 (en) |
CY (1) | CY2411B1 (en) |
CZ (1) | CZ291041B6 (en) |
DE (1) | DE69420266T2 (en) |
DK (1) | DK0700290T3 (en) |
EC (1) | ECSP941088A (en) |
ES (1) | ES2136198T3 (en) |
FR (1) | FR2705569B1 (en) |
GB (2) | GB9310756D0 (en) |
GR (1) | GR3031669T3 (en) |
HR (2) | HRP940315B1 (en) |
HU (1) | HU227121B1 (en) |
IE (1) | IE80632B1 (en) |
IL (1) | IL109749A (en) |
IS (1) | IS1868B (en) |
IT (1) | IT1272990B (en) |
MY (1) | MY111445A (en) |
NO (1) | NO306448B1 (en) |
NZ (1) | NZ267415A (en) |
PE (1) | PE13395A1 (en) |
PL (1) | PL175578B1 (en) |
RU (1) | RU2132684C1 (en) |
SA (1) | SA94150003B1 (en) |
SG (1) | SG48119A1 (en) |
SI (1) | SI0700290T1 (en) |
WO (1) | WO1994027599A1 (en) |
ZA (1) | ZA943593B (en) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1468685A3 (en) * | 1998-06-15 | 2004-12-15 | Sepracor Inc. | Use of optically pure (+)-norcisapride for treating apnea, bulimia and other disorders |
CN1312716A (en) * | 1998-06-15 | 2001-09-12 | 塞普拉科有限公司 | Use of optically pure (-)-norcisapride in treatment of apnea, bulimta and other disorders |
EP1464333A3 (en) * | 1998-06-15 | 2004-12-15 | Sepracor Inc. | Use of optically pure (-) norcisapride in the treatment of apnea, bulimia, and other disorders |
SK19052000A3 (en) * | 1998-06-15 | 2001-06-11 | Sepracor, Inc. | Use of optically pure (+)-norcisapride for treating apnea, bulimia and other disorders |
US6362202B1 (en) | 1999-03-02 | 2002-03-26 | Sepracor Inc. | Methods and compositions using (−) norcisapride in combination with proton pump inhibitors or H2 receptor antagonists |
US6353005B1 (en) | 1999-03-02 | 2002-03-05 | Sepracor, Inc. | Method and compositions using (+) norcisapride in combination with proton pump inhibitors or H2 receptor antagonist |
ATE547101T1 (en) * | 2000-08-04 | 2012-03-15 | Dmi Biosciences Inc | METHOD OF USE OF DIKETOPIPERAZINES AND COMPOSITIONS CONTAINING SAME |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4983621A (en) * | 1988-07-07 | 1991-01-08 | Glaxo Group Limited | Medicaments |
WO1992004012A1 (en) * | 1990-09-10 | 1992-03-19 | Alza Corporation | Antiemetic therapy |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4695578A (en) * | 1984-01-25 | 1987-09-22 | Glaxo Group Limited | 1,2,3,9-tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, composition containing them, and method of using them to treat neuronal 5HT function disturbances |
DE3502508A1 (en) * | 1984-01-25 | 1985-08-14 | Glaxo Group Ltd., London | HETEROCYCLIC COMPOUNDS |
GB8627909D0 (en) * | 1986-11-21 | 1986-12-31 | Glaxo Group Ltd | Medicaments |
-
1993
- 1993-05-25 GB GB939310756A patent/GB9310756D0/en active Pending
-
1994
- 1994-05-17 EC EC1994001088A patent/ECSP941088A/en unknown
- 1994-05-17 GB GB9409835A patent/GB2279008B/en not_active Expired - Lifetime
- 1994-05-17 SG SG1996007139A patent/SG48119A1/en unknown
- 1994-05-19 IS IS4168A patent/IS1868B/en unknown
- 1994-05-20 MY MYPI94001305A patent/MY111445A/en unknown
- 1994-05-23 AP APAP/P/1994/000643A patent/AP544A/en active
- 1994-05-23 PE PE1994242905A patent/PE13395A1/en not_active IP Right Cessation
- 1994-05-23 IE IE940420A patent/IE80632B1/en not_active IP Right Cessation
- 1994-05-23 HR HR940315A patent/HRP940315B1/en not_active IP Right Cessation
- 1994-05-23 CO CO94021615A patent/CO4230094A1/en unknown
- 1994-05-24 CA CA002162919A patent/CA2162919C/en not_active Expired - Lifetime
- 1994-05-24 DK DK94918355T patent/DK0700290T3/en active
- 1994-05-24 ES ES94918355T patent/ES2136198T3/en not_active Expired - Lifetime
- 1994-05-24 KR KR1019950705280A patent/KR100297212B1/en not_active IP Right Cessation
- 1994-05-24 PL PL94311721A patent/PL175578B1/en unknown
- 1994-05-24 HU HU9503375A patent/HU227121B1/en unknown
- 1994-05-24 ZA ZA943593A patent/ZA943593B/en unknown
- 1994-05-24 SI SI9430263T patent/SI0700290T1/en unknown
- 1994-05-24 JP JP7500204A patent/JP2965703B2/en not_active Expired - Lifetime
- 1994-05-24 AT AT94918355T patent/ATE183643T1/en active
- 1994-05-24 WO PCT/EP1994/001652 patent/WO1994027599A1/en active IP Right Grant
- 1994-05-24 US US08/537,950 patent/US5741806A/en not_active Expired - Lifetime
- 1994-05-24 IT ITRM940322A patent/IT1272990B/en active IP Right Grant
- 1994-05-24 CZ CZ19953085A patent/CZ291041B6/en not_active IP Right Cessation
- 1994-05-24 EP EP94918355A patent/EP0700290B1/en not_active Expired - Lifetime
- 1994-05-24 FR FR9406252A patent/FR2705569B1/en not_active Expired - Lifetime
- 1994-05-24 RU RU95122578A patent/RU2132684C1/en active
- 1994-05-24 BE BE9400528A patent/BE1007158A3/en not_active IP Right Cessation
- 1994-05-24 IL IL10974994A patent/IL109749A/en not_active IP Right Cessation
- 1994-05-24 AU AU69709/94A patent/AU680918B2/en not_active Expired
- 1994-05-24 DE DE69420266T patent/DE69420266T2/en not_active Expired - Lifetime
- 1994-05-24 NZ NZ267415A patent/NZ267415A/en not_active IP Right Cessation
- 1994-05-24 CN CN94192243A patent/CN1106194C/en not_active Expired - Lifetime
- 1994-06-12 SA SA94150003A patent/SA94150003B1/en unknown
-
1995
- 1995-11-24 NO NO954783A patent/NO306448B1/en not_active IP Right Cessation
-
1996
- 1996-09-19 BR BR1100046-5A patent/BR1100046A/en active IP Right Grant
-
1997
- 1997-06-09 HR HR970315A patent/HRP970315A2/en not_active Application Discontinuation
-
1999
- 1999-10-27 GR GR990402759T patent/GR3031669T3/en unknown
-
2000
- 2000-06-06 CY CY0000022A patent/CY2411B1/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4983621A (en) * | 1988-07-07 | 1991-01-08 | Glaxo Group Limited | Medicaments |
WO1992004012A1 (en) * | 1990-09-10 | 1992-03-19 | Alza Corporation | Antiemetic therapy |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AP544A (en) | Compositions for rectal administration | |
US5705506A (en) | Pharmaceutical compositions of alkylsulphonamides 5HT1 agonists for rectal administration | |
AU626010B2 (en) | Medicaments | |
EP0345931A1 (en) | Certain PAF antagonist/antihistamine combinations and methods | |
EP0567498A1 (en) | Pharmaceutical composition containing granisetron and dexamethasone | |
JPH05294830A (en) | Pharmaceutical composition containing triazole derivative and used for rectal administration |