GB2262036A - Anti inflammatories or analgesics - Google Patents
Anti inflammatories or analgesics Download PDFInfo
- Publication number
- GB2262036A GB2262036A GB9225174A GB9225174A GB2262036A GB 2262036 A GB2262036 A GB 2262036A GB 9225174 A GB9225174 A GB 9225174A GB 9225174 A GB9225174 A GB 9225174A GB 2262036 A GB2262036 A GB 2262036A
- Authority
- GB
- United Kingdom
- Prior art keywords
- bismuth citrate
- analgesia
- treating
- ranitidine bismuth
- compound
- 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.)
- Granted
Links
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
- A61K31/415—1,2-Diazoles
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
Compositions contain (i) ranitidine bismuth citrate and (ii) a non-steroidal anti-inflammatory drug for treating or preventing inflammatory conditions and for analgesia. Exemplified as the NSAID are indomethacin or ibuprofen.
Description
c---5 2 MEDICAMENTS FOR TREATING INFLAMMATORY CONDITIONS OR FOR ANALGESIA
The present invention relates to improvements in the treatment of inflammatory conditions and for analgesia. More particularly it relates to the co- administration of a non-steroidal anti-inflammatory drug with a salt formed between Z:' ranitidine and a complex of bismuth with a carboxylic acid.
Systemic non-steroidal anti-inflammatory drugs, such as aspirin, indomethacin, ibuprofen and piroxicam, are known to give rise to undesirable side effects. In particular, they are known to be ulcerogenic and call thus, for example, give rise to gastric and/or duodenal ulceration when administered orally. This side effect may be further enhanced in combination with other factors such as stress and smoking. Since in some treatments these compounds may have to be used for an extended period, such side effects can prove a serious disadvantage.
In our UK Patent Specification No. 2220937B we describe and claim salts formed between ranitidine and a complex of bismuth with a carboxylic acid, particularly tartaric acid and, more especially, citric acid. One such salt is N-[2-[[[5 [ (dimethylamino) methyl] -2-furanyl] methyl] thio] ethyl] - N'-m ethyl - 2- nitro- 1, 1 - ethenediamine 2-hydroxy-1,2,3-propanetricarboxylate bismuth (3+) complex, also known as ranitidine bismuth citrate.
The salts disclosed in UK Patent Specification No. 2220937B possess the H) antagonist antisecretory properties associated with ranitidine, together with antibacterial activity against Helicobacter pylori (formerly Campylobacter pylori). In addition, such salts possess cytoprotective properties and display activity against the human gastric pepsins with preferential inhibition of pepsin 1, a pepsin isozyme associated with peptic ulcer. The salts disclosed in UK Patent Specification No.
2220937B thus possess a particularly advantageous combination of properties for the treatment of gastrointestinal disorders, especially peptic ulcer disease (e.g.
HA162 gastric and duodenal ulceration) and other gastroduodenal conditions, for example gastritis and non-ulcer dyspepsia.
Tests in animals and humans have now shown that mucosal lesions of the gastrointestinal tract caused by non-steroidal anti-inflammatory drugs are significantly reduced by administering ranitidine bismuth citrate. In particular, we have demonstrated in rats the ability of ranitidine bismuth citrate to prevent indomethacin induced gastric antral ulceration using a modification of the method of Satoh et al., Gastroenterology (1981), 81, 719-725. In this test ranitidine bismuth citrate was markedly more potent than both ranitidine hydrochloride and tripotassium dicitrato bismuthate as DeNolTM. A recently published human clinical study (N. Hudson et al., Gut 1992, 33 supplement, s47) also demonstrates that ranitidine bismuth citrate confers substantial protection from aspirin- induced injury to the gastric mucosa.
The present invention thus provides, in one aspect, the use of (i) ranitidine bismuth citrate and (ii) a non-steroidal anti-inflammatory drug in the manufacture of medicaments for simultaneous, separate or sequential use in treating or preventing inflammatory conditions or for analgesia.
In a further, or alternative, aspect the present invention provides the use of ranitidine bismuth citrate in the manufacture of medicaments to prevent gastrointestinal damage caused by non-steroidal anti-inflammatory drugs. - Combination therapy according to the present invention may be used in the treatment of inflammatory conditions, particularly acute and chronic musculo skeletal inflammatory conditions such as. rheumatoid and osteo-arthritis and ankylosing spondylitis and for analgesia in conditions such as dysmenorrhoea, especially where the use of the anti-inflammatory drug is limited by gastrointestinal side effects. As stated above, co-administration of ranitidine bismuth citrate with a systematic non-steroidal anti-inflammatory drug may also be used to prevent gastrointestinal damage caused by non-steroidal anti-inflammatory drugs. Such, gastrointestinal damage includes duodenal and/or gastric ulceration, non- steroidal HA162 anti-inflammatory drug associated gastritis and gastric erosions, and non- steroidal anti-inflammatory drug associated mucosal damage to the small intestine.
Suitable systemic non-steroidal anti-inflammatory drugs which may be employed in the invention generally also show analgesic activity and include, for example, aspirin, indomethacin, ibuprofen, piroxicam, fenoprofen, ketoprofen, naproxen, mefenamic acid, diflunisal, benorylate, azapropazone, diclofenac, fenbufen, feprazone, fenclofenac, flufenamic acid, flurbiprofen, oxyphenbutazone, phenylbutazone, sulindac and tolmetin.
The ranitidine bismuth citrate and the anti-inflammatory drug are preferably co-administered in the form of separate pharmaceutical compositions for simultaneous and/or sequential use. Alternatively the ranitidine bismuth citrate and the anti-inflammatory drug may be administered as a single pharmaceutical composition for oral use comprising effective amounts of the active ingredients.
Thus, according to a further aspect, the invention provides a product containing (i) ranitidine bismuth citrate and (ii) a non-steroidal antfinflammatory drug as a combined preparation for simultaneous, separate or sequential use in treating or preventing inflammatory conditions or for analgesia.
When the ranitidine bismuth citrate and the non-steroidal antiinflammatory are administered as separate preparations, the anti-inflammatory may be provided in any convenient formulation, such as in the manner known in the art and/or commercially for the compound concerned. Administration of both the ranitidine bismuth citrate and the non-steroidal anti-inflammatory by the oral route is preferred, although the anti-inflammatory, where appropriate, may also be given by another route, for example parenterally (e.g. intravenously) or rectally (e.g. by suppository).
The ranitidine bismuth citrate may conveniently be formulated as tablets (including chewable tablets), capsules (of either the hard or soft type), or as a liquid preparation, as described for example in UK Patent Specification Nos. _222093713 and 2248185A. Tablets are generally preferred.
HA162 As stated hereinabove, ranitidine bismuth citrate and the non-steroidal antiinflammatory drug may be administered as a single phar,-naceutical composition for oral use. Thus, according to a further aspect the invention provides a pharmaceutical composition, for oral use in human or veterinary medicine, comprising ranitidine bismuth citrate and a non-steroidal anti-inflammatory drug, together, where appropriate, with a pharmaceutically acceptable carrier or excipient.
Suitable additional carriers or excipients include binding agents (e.g. pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylceRulose); fillers (e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g..starch or sodium starch glycollate); or wetting agents (e.g. sodium lauryl sulphate). An alkaline. salt of the type described in UK Patent Specification No. -2248185A. may be added to improve the rate of disintegration and/or dissolution of the composition.
The compositions may be prepared according to conventional techniques well known in the pharmaceutical industry. Thus, for example, the ranitidine bismuth citrate and the non-steroidal anti-inflammatory drug may be admixed together, if desired, with suitable carriers or excipients. Tablets may be prepared, for example, by direct compression or wet granulation of such a mixture. Capsules may be -prepared by filling the blend along with suitable carriers or excipients into gelatin capsules, using a suitable filling machine. Tablets may be coated by methods well known in-the-art. The preparations may also contain flavouring, colouring and/or sweetening agents as appropriate.
When ranitidine bismuth citrate and the non-steroidal anti-inflammatory drug are administered as a single pharmaceutical composition for oral use the composition is preferably in the form of a capsule or, more particularly, a tablet.
The compositions for use according to the invention may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredients. The pack may for example comprise metal or plastic fbiL such as a blister pack. Where the ranitidine bismuth citrate and. the 1 HA162 non-steroidal anti-inflammatory drug are intended for administration as separate compositions these may be presented in the form of, for example, a twin pack.
Thus, according to a further aspect the present invention provides a twincontainer pack for use in treating or preventing inflammatory conditions or for analgesia, one of the containers containing ranitidine bismuth citrate and the other containing a non-steroidal anti-inflammatory drug.
The doses at which the ranitidine bismuth citrate and the non-steroidal antiinflammatory may be administered to man (of approximately 70kg body weight) will depend on the route of administration of the antiinflammatory and on the nature and severity of the condition being treated. It will also be appreciated that it may be necessary to make routine variations to the dosage depending on the age and weight of the patient.
A proposed dosage of ranitidine bismuth citrate for use according to the invention is 150mg to 1.5g, preferably 200 - 800mg per unit dose. The unit dose may be administered, for example, 1 to 4 times per day, preferably once or twice per day.
The non-steroidal anti-inflammatory may conveniently be administered at doses within the normal dosage range at which the compound is therapeutically effective, for example 50mg-lg of aspirin, 10 -100 mg of indomethacin, 5 - 50 mg of piroxicam, 100-500mg of ibuprofen and 200800mg of mefenamic acid per dosage unit taken one or more times daily in accordance with the normal dosage regime for the drug in question.
In a further aspect, the present invention provides a method of treating inflammatory conditions or for analgesia in a human or animal subject, which comprises administering to said subject effective amounts of ranitidine bismuth citrate and a non-steroidal anti-inflammatory drug.
In another, or alternative, aspect the present invention provides a method of treating gastrointestinal damage caused by non-steroidal antiinflammatory drugs in. a human or animal subject, which comprises administering to said subject an effective amount of ranitidine bismuth citrate.
HA162 References herein to treatment include prophylactic treatment as well as the alleviation of acute symptoms.
The methods of the present invention comprise administering the nonsteroidal anti-inflammatory drug and ranitidine bismuth citrate either concurrently or non-concurrently. As used herein, concurrent administration means that the agents are given within 24 hours of each other, whereas non-concurrent administration means that the agents are given more than 24 hours apart. When the agents are administered concurrently, it may be preferable to administer the agents within about 1 hour of each other or, more preferably, within about 5 minutes of each other.
For the methods of the present invention, the duration of administration of the agents during either concurrent or non-concurrent dosing will vary according to the specific condition being treated.
The following examples illustrate pharmaceutical compositions for oral use containing both ranitidine bismuth citrate and a suitable non-steroidal antiinflammatory drug.
Example 1 TABLETS (a) Ranitidine bismuth citrate Ibuprofen Lactose Hydroxypropyl methylcellulose Sodium starch glycollate Magnesium stearate Compression weight mg/tablet 400.00 400.00 200.00 5.00 30.00 10.00 1045.00 The ranitidine bismuth. citrate and ibuprofen are sieved through a 250,vm sieve and blended with the lactose. This mix is granulated with a solution of the HA162 hydroxypropyl methylcellulose. The granules are dried, screened and blended with the sodium starch glycollate and the magnesium stearate. The lubricated granules are compressed into tablets using 15.0mrn punches.
mp/tablet
400.00 50.00 114.00 30.00 6.00 (b) Ranitidine bismuth citrate Indomethacin Microcrystalline cellulose Anhydrous sodium carbonate Magnesium stearate Compression weight 600.00 The ranitidine bismuth citrate and indomethacin are blended with the m icrocrys tall ine cellulose, sodium carbonate and magnesium stearate and compressed using 12.5mm punches.
Example 2 CAPSULES (a) Ranitidine bismuth citrate Ibuprofen Starch 1500 Magnesium stearate Fill weight 800.00 A form of directly compressible starch supplied by Colorcon Ltd, Orpington, Kent.
Capsule 200.00 196.00 4.00 The ranitidine bismuth citrate and ibuprofen are sieved through a 25011m sieve, and blended with the Starch 1500 and magnesium stearate. The resultant mix is filled into size 0 hard gelatin capsules using a suitable filling machine.
HA162 rng/capsule (b) Ranitidine bismuth citrate 200.00 Indomethacin 50.00 Starch 1500 48.50 Magnesium stearate 1.50 Fill weight 300.00 The ranitidine bismuth citrate and indomethacin are sieved through a 250grn sieve and blended with the Starch 1500 and magnesium stearate. The resultant mix is filled into size -2 hard gelatin capsules using a suitable filling machine.
Example 3 _INHIBITION OF INDOMETHACIN-INDUCED GASTRIC LESIONS IN THE RAT The ability of ranitidipe bismuth citrate to prevent indomethacin Anduced gastric antral ulceration was compared with that of ranitidine hydrochloride and De NoITM.
Female rats, which had been fasted for 24 hours and then re-fed, received ranitidine bismuth citrate Q to 10Orng/kg), ranitidine hydrochloride (10 to 10Orng/kg) or De-NoITM (3 to 10Ornglkg) by oral gavage. Ranitidine bismuth citrate was administered as a suspension and the other test compounds as solutions.
Thirty minutes after dosing with the test compound, animals received indomethacin (60mg/kg sc) as an ulcerogenic stimulus and after a further 6 hours the animals were killed and the antral region assessed macroscopically for damage.
Results are presented in the table below. Ranitidine bismuth citrate produced a dose-related inhibition- of indomethacin-induced lesions and was relatively potent, an ED50 value of 4.5rng/kg po being calculated. Ranitidine hydrochloride and De NoITM were markedly less potent.
HA162 ED5n Values for Inhibition of Indomethacin - Induced Antral Ulceration Compound Ranitidine Ranitidine Bismuth Citrate Hydrochloride ED50 4.5 23.4 mglkg p.o.
95% confidence 0.5-10.7 16.0-33.0 limits De-NoITM 43.2 -216-93.0 HA162
Claims (12)
1. The use of (i) ranitidine bismuth citrate and (ii) a nonsteroidal antiinflammatory drug in the manufacture of medicaments for simultaneous, separate or sequential use in treating or preventing inflammatory conditions or for analgesia.
2. The -use of ranitidine bismuth citrate in the manufacture of medicaments to prevent gastrointestinal damage caused by non-steroidal anti-inflammatory drugs.
The use according to Claim 1 in which the compounds (i) and (ii) are presented as separate compositions for said use.
4. - A product containing compounds (i) and (ii) as defined in Claim 1 as a combined preparation for simultaneous, separate or sequential use in treating or preventing inflammatory conditions or for analgesia.
- -
5. A pharmaceutical composition, for oral use, which comprises both a compound (i) and 25. a compound (ii) as defined-in Claim l., together with a pharmaceutical carrier or excipient. -
6. A use, product - or composition according to any preceding claim in which the non-steroidal anti-inflammatory drug is selected from aspirin, indomethacin, ibuproflen, piroxicam, fenoprofen, ketoprofen, naproxen, mefenamic acid, diflunisal, benorylate, azapropazone, diclofenac, fenbufen, feprazone, fenclofenac, flufenamic acid, flurbiprofen, oxyphenbutazone, phenylbutazone, sulindac and tolmetin.
7. A use or produc.t according to any preceding claim in which compounds (i) and (ii) are in forms suitable for oral administration.
8. A use or product according to any preceding claim in which compound (i) is formulated as a tablet.
t:
C; 1 t HA162 11
9. A use or product according to Claim 8 in which compound (i) is administered at a dosage of 200-80Orng per unit dose.
10. A twin-container pack for use in treating or preventing inflammatory conditions or for analgesia, one of the containers containing (i) and the other containing (ii) as defined in the preceding claims.
11. A composition according to Claim 5 or Claim 6 or a pack according to Claim 10, in association with instructions for the use of both (i) and (ii) in treating or preventing inflammatory conditions or for analgesia.
12. A method for the preparation of a composition according to Claim 5 or Claim 6 which comprises admixing (i) and (ii) together, if desired, with suitable carriers or excipients.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919126027A GB9126027D0 (en) | 1991-12-06 | 1991-12-06 | Medicaments |
| GB929206083A GB9206083D0 (en) | 1992-03-20 | 1992-03-20 | Medicaments |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB9225174D0 GB9225174D0 (en) | 1993-01-20 |
| GB2262036A true GB2262036A (en) | 1993-06-09 |
| GB2262036B GB2262036B (en) | 1996-01-03 |
Family
ID=26299971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9225174A Expired - Fee Related GB2262036B (en) | 1991-12-06 | 1992-12-02 | Medicaments for treating inflammatory conditions or for analgesia |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US5466436A (en) |
| EP (1) | EP0550083B1 (en) |
| JP (1) | JPH05246853A (en) |
| KR (1) | KR930009605A (en) |
| AP (1) | AP324A (en) |
| AT (1) | AT401468B (en) |
| AU (1) | AU664574B2 (en) |
| BE (1) | BE1007268A3 (en) |
| CA (1) | CA2084568A1 (en) |
| CH (1) | CH685537A5 (en) |
| CZ (1) | CZ358092A3 (en) |
| DE (1) | DE69228738D1 (en) |
| DK (1) | DK0550083T3 (en) |
| ES (1) | ES2130152T3 (en) |
| FR (1) | FR2684554B1 (en) |
| GB (1) | GB2262036B (en) |
| GR (1) | GR3030426T3 (en) |
| IE (1) | IE922866A1 (en) |
| IL (1) | IL103978A (en) |
| IT (1) | IT1256697B (en) |
| LU (1) | LU88196A1 (en) |
| MX (1) | MX9207008A (en) |
| MY (1) | MY108146A (en) |
| NO (1) | NO303670B1 (en) |
| NZ (1) | NZ245365A (en) |
| PH (1) | PH31380A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998022118A1 (en) * | 1996-11-22 | 1998-05-28 | The Procter & Gamble Company | Compositions for the treatment of gastrointestinal disorders containing bismuth and nsaid |
| WO1998022117A1 (en) * | 1996-11-22 | 1998-05-28 | The Procter & Gamble Company | Compositions for the treatment of gastrointestinal disorders containing bismuth, and nsaid and one or more antimicrobials |
| US5817289A (en) * | 1995-01-26 | 1998-10-06 | Nycomed Imaging As | Non-cluster type bismuth compounds |
| US6117412A (en) * | 1995-01-26 | 2000-09-12 | Nycomed Imaging As | Non-cluster type bismuth compounds |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0000774D0 (en) * | 2000-03-08 | 2000-03-08 | Astrazeneca Ab | New formulation |
| SE0000773D0 (en) * | 2000-03-08 | 2000-03-08 | Astrazeneca Ab | New formulation |
| CZ20032398A3 (en) * | 2001-03-08 | 2004-02-18 | Astrazeneca Ab | Novel use of 6-carboxamidoimidazo[1,2-a]pyridine derivatives |
| IL159129A0 (en) | 2001-06-01 | 2004-05-12 | Pozen Inc | PHARMACEUTICAL COMPOSITIONS FOR THE COORDINATED DELIVERY OF NSAIDs |
| US8206741B2 (en) | 2001-06-01 | 2012-06-26 | Pozen Inc. | Pharmaceutical compositions for the coordinated delivery of NSAIDs |
| SE0102993D0 (en) | 2001-09-07 | 2001-09-07 | Astrazeneca Ab | New self emulsifying drug delivery system |
| US20080021078A1 (en) * | 2006-07-18 | 2008-01-24 | Horizon Therapeutics, Inc. | Methods and medicaments for administration of ibuprofen |
| US8067451B2 (en) * | 2006-07-18 | 2011-11-29 | Horizon Pharma Usa, Inc. | Methods and medicaments for administration of ibuprofen |
| US20080020040A1 (en) * | 2006-07-18 | 2008-01-24 | Horizon Therapeutics, Inc. | Unit dose form for administration of ibuprofen |
| US20070043096A1 (en) * | 2005-07-18 | 2007-02-22 | Horizon Therapeutics, Inc. | Unit dose form with ibuprofen-famotidine admixture |
| US8067033B2 (en) | 2007-11-30 | 2011-11-29 | Horizon Pharma Usa, Inc. | Stable compositions of famotidine and ibuprofen |
| WO2008027963A2 (en) * | 2006-08-31 | 2008-03-06 | Horizon Therapeutics, Inc. | Nsaid dose unit formulations with h2-receptor antagonists and methods of use |
| AU2009290712A1 (en) | 2008-09-09 | 2010-03-18 | Astrazeneca Ab | Method for delivering a pharmaceutical composition to patient in need thereof |
| WO2010151216A1 (en) | 2009-06-25 | 2010-12-29 | Astrazeneca Ab | Method for treating a patient at risk for developing an nsaid-associated ulcer |
| CN104519888A (en) | 2011-12-28 | 2015-04-15 | 波曾公司 | Improved compositions and methods for delivery of omeprazole plus acetylsalicylic acid |
| CN110893233A (en) * | 2019-12-19 | 2020-03-20 | 川北医学院附属医院 | Application of irisin in preparation of anti-inflammatory drugs |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992011849A1 (en) * | 1991-01-14 | 1992-07-23 | The Procter & Gamble Company | Swallowable pharmaceutical compositions |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4464679A (en) * | 1981-07-06 | 1984-08-07 | Rca Corporation | Method and apparatus for operating a microprocessor in synchronism with a video signal |
| CY1398A (en) * | 1981-09-04 | 1987-12-18 | Glaxo Group Ltd | Pharmaceutical compositions containing non-steroidal anti-inflammatory agents |
| CA1211374A (en) * | 1982-05-14 | 1986-09-16 | Eszter Cholnoky | Pharmaceutical compositions containing more active ingredients |
| US4757060A (en) * | 1986-03-04 | 1988-07-12 | Bristol-Myers Company | Non-steroidal anti-inflammatory compositions protected against gastrointestinal injury with a combination of certain H1 and H2, receptor blockers |
| GB8625325D0 (en) * | 1986-10-22 | 1986-11-26 | Glaxo Group Ltd | Chemical compounds |
| IL85472A (en) * | 1987-03-09 | 1991-06-30 | Procter & Gamble | Pharmaceutical compositions for treating gastrointestinal disorders |
| ATE81011T1 (en) * | 1987-03-09 | 1992-10-15 | Procter & Gamble | COMPOSITIONS AND THEIR USE IN THE TREATMENT OF GASTROINTESTINAL DISORDERS. |
| CH679582A5 (en) * | 1988-07-18 | 1992-03-13 | Glaxo Group Ltd | |
| NZ235877A (en) * | 1989-11-02 | 1992-09-25 | Mcneil Ppc Inc | Composition comprising acetaminophen or nsaid and an h 1 or h 2 receptor blocker and/or proton pump inhibitor for treating overindulgence |
| GB9019875D0 (en) * | 1990-09-11 | 1990-10-24 | Glaxo Group Ltd | Pharmaceutical compositions |
-
1992
- 1992-11-27 EP EP92203674A patent/EP0550083B1/en not_active Expired - Lifetime
- 1992-11-27 ES ES92203674T patent/ES2130152T3/en not_active Expired - Lifetime
- 1992-11-27 DE DE69228738T patent/DE69228738D1/en not_active Expired - Lifetime
- 1992-11-27 DK DK92203674T patent/DK0550083T3/en active
- 1992-12-02 GB GB9225174A patent/GB2262036B/en not_active Expired - Fee Related
- 1992-12-03 PH PH45371A patent/PH31380A/en unknown
- 1992-12-04 JP JP4325308A patent/JPH05246853A/en active Pending
- 1992-12-04 NO NO924704A patent/NO303670B1/en unknown
- 1992-12-04 NZ NZ245365A patent/NZ245365A/en unknown
- 1992-12-04 IT ITRM920869A patent/IT1256697B/en active IP Right Grant
- 1992-12-04 AU AU29863/92A patent/AU664574B2/en not_active Ceased
- 1992-12-04 MX MX9207008A patent/MX9207008A/en not_active IP Right Cessation
- 1992-12-04 CH CH3737/92A patent/CH685537A5/en unknown
- 1992-12-04 LU LU88196A patent/LU88196A1/en unknown
- 1992-12-04 CZ CS923580A patent/CZ358092A3/en unknown
- 1992-12-04 FR FR9214642A patent/FR2684554B1/en not_active Expired - Fee Related
- 1992-12-04 IL IL103978A patent/IL103978A/en not_active IP Right Cessation
- 1992-12-04 BE BE9201070A patent/BE1007268A3/en not_active IP Right Cessation
- 1992-12-04 AT AT0240692A patent/AT401468B/en not_active IP Right Cessation
- 1992-12-04 MY MYPI92002235A patent/MY108146A/en unknown
- 1992-12-04 CA CA002084568A patent/CA2084568A1/en not_active Abandoned
- 1992-12-04 KR KR1019920023309A patent/KR930009605A/en not_active Application Discontinuation
- 1992-12-04 AP APAP/P/1992/000453A patent/AP324A/en active
- 1992-12-04 IE IE286692A patent/IE922866A1/en not_active Application Discontinuation
-
1993
- 1993-12-17 US US08/168,231 patent/US5466436A/en not_active Expired - Fee Related
-
1999
- 1999-06-04 GR GR990401510T patent/GR3030426T3/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992011849A1 (en) * | 1991-01-14 | 1992-07-23 | The Procter & Gamble Company | Swallowable pharmaceutical compositions |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5817289A (en) * | 1995-01-26 | 1998-10-06 | Nycomed Imaging As | Non-cluster type bismuth compounds |
| US6117412A (en) * | 1995-01-26 | 2000-09-12 | Nycomed Imaging As | Non-cluster type bismuth compounds |
| US6303101B1 (en) | 1995-01-26 | 2001-10-16 | Nycomed Imaging As | Bismuth compounds |
| WO1998022118A1 (en) * | 1996-11-22 | 1998-05-28 | The Procter & Gamble Company | Compositions for the treatment of gastrointestinal disorders containing bismuth and nsaid |
| WO1998022117A1 (en) * | 1996-11-22 | 1998-05-28 | The Procter & Gamble Company | Compositions for the treatment of gastrointestinal disorders containing bismuth, and nsaid and one or more antimicrobials |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19991202 |