GB2287404A - Antiinflammatory and analgesic compositions - Google Patents
Antiinflammatory and analgesic compositions Download PDFInfo
- Publication number
- GB2287404A GB2287404A GB9420055A GB9420055A GB2287404A GB 2287404 A GB2287404 A GB 2287404A GB 9420055 A GB9420055 A GB 9420055A GB 9420055 A GB9420055 A GB 9420055A GB 2287404 A GB2287404 A GB 2287404A
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- GB
- United Kingdom
- Prior art keywords
- inflammatory
- substance
- antiinflammatory
- pain
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000203 mixture Substances 0.000 title claims abstract description 14
- 230000000202 analgesic effect Effects 0.000 title abstract description 3
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 16
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims abstract description 6
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Compositions for treating inflammatory diseases and pain comprise a substance P receptor antagonist and an antiinflammatory/analgesic compound. The substance P receptor antagonists include NK-1 antagonists within their scope. Typical antiinflammatories/analgesics are acetaminophen, aspirin, NSAID's, codiene, fentanyl, sufentanyl, morphine, ibuprofen, piroxicam, naproxen, sunlindac, ketorolac, or indomethacin. Administration may be oral, parenteral or topical.
Description
ANTI-INFLAMMATORY COMPOSITIONS
Background of the Invention
This invention relates to pharmaceutical compositions for the prevention and treatment of inflammatory diseases and pain, comprising substance P receptor antagonists, and to a method for such prevention and treatment.
The interactions of certain pathways with that of substance P has been described. For instance, Malmberg et al., Science, 257,1276 (1992) refers to the action of nonsteroidal anti-inflammatory drugs (NSAIDs) by blocking the excessive sensitivity to pain (hyperalgesia) induced by the activation of substance P receptors. Dougherty et a Pain, 47, 85 (1991) describes potentiation and prolongation of N-methyl-Daspartic acid (NMDA) responses by substance P based on recordings from spinothalamic neurons.
Substance P receptor antagonists, which include NK-1 antagonists, are known to be of value in the treatment of inflammatory diseases and pain and are disclosed in
U.S. Patent No. 5,162,339 and other publications.
Summarv of the Invention
This invention relates to a pharmaceutical composition for the prevention or treatment of pain or inflammatory diseases which comprises a substance P receptor antagonist and an anti-inflammatory or analgesic agent.
The invention also relates to a method for prevention or treatment of pain or inflammatory diseases by administering to a patient in need of such prevention or treatment an effective amount of a substance P receptor antagonist and an antiinflammatory or analgesic agent.
In a preferred embodiment of the invention said anti-inflammatory or analgesic agent is selected from the group consisting of an opiate agonist, a lipoxygenase inhibitor, a cyclooxygenase inhibitor, an NMDA antagonist, an inhibitor of nitric oxide and an inhibitor of the synthesis of nitric oxide.
Detailed Description of the invention
The invention makes use of substance P receptor antagonists. Examples of such compounds include those described in U.S. Patents 5,162,339 and 5,232,929, WO 92/06079, 92/15585, 93/0330 and 93/06099, and European Patent Publication 533 280, which are all incorporated herein by reference.
The invention further makes use of anti-inflammatory and analgesic agents, not including substance P receptor antagonists. Examples of analgesic and antiinflammatory agents include those listed in the Physician's Desk Reference (1993) under the headings: analgesics and anti-inflammatory agents. Also included are antiinflammatory compounds that work by inhibiting the production of inflammatory mediators, e.g, corticosteroids.
More specifically, the anti-inflammatory or analgesic agents of use in the invention include but are not limited to acetaminophen, aspirin, NSAIDs, and narcotics such as codeine, fentanyl, sufentanyl, and morphine. Specific anti-inflammatory agents include ibuprofen, Feldenes (piroxicam), NaprosynX (naproxen), ketorolac tromethamine, indomethacin, Clinoril$ (sulindac), etc.
The invention includes combinations of substance P antagonists and two or more anti-inflammatory agents or an anti-inflammatory and an analgesic agent.
The invention is for the prevention and treatment of inflammatory diseases including arthritis, psoriasis, asthma and inflammatory bowel disease, and acute and chronic pain, such as postoperative pain, cancer-related pain, neuropathic pain syndromes and fibromyalgia.
The pharmaceutical composition of the invention may be administered by the oral, parenteral or topical routes. In general, these compositions are most desirably administered in dosages ranging from about 5.0 mg up to about 1500 mg per day, although variations will necessarily occur depending upon the weight and condition of the subject being treated and the particular route of administration chosen. However, a dosage level that is in the range of about 0.07 mg to about 21 mg per kg of body weight per day is most desirably employed. Variations may nevertheless occur depending upon the subject being treated and the individual's response to said medicament, as well as on the type of pharmaceutical formulation chosen and the time period and interval at which such administration is carried out. In some instances, dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger doses may be employed without causing any harmful side effect, provided that such larger doses are first divided into several small doses for administration throughout the day.
The anti-inflammatory or analgesic agent present in the compositions of the invention may be administered in conventional amounts of about 5 to about 1000 mg per day, or in below conventional amounts of 10 to 50% of the conventional amounts may be used.
The compositions of the invention may be administered alone or in combination with pharmaceutically acceptable carriers or diluents by either of the three routes previously indicated, and such administration may be carried out in single or multiple doses. More particularly, the compositions of this invention can be administered in a wide variety of different dosage forms, i.e., they may be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hard candies, powders, sprays, creams, salves, suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups, and the like. Such carriers include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc. Moreover, oral pharmaceutical compositions can be suitably sweetened and/or flavored. In general, the therapeutically-effective compositions of the invention are present in such dosage forms at concentration levels ranging from about 5.0% to about 70% by weight.
For oral administration, tablets containing various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate and glycine may be employed along with various disintegrants such as starch, preferably corn, potato or tapioca starch, alginic acid and certain complex silicates, together with granulation binders like polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for tabletting purposes. Solid compositions of a similar type may also be employed as fillers in gelatin capsules; preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene glycols.
When aqueous suspensions and/or elixirs are desired for oral administration, the active ingredient may be combined with various sweetening or flavoring agents, coloring matter or dyes, and, if so desired, emulsifying and/or suspending agents as well, together with such diluents as water, ethanol, propylene glycol, glycerin and various like combinations thereof.
For parenteral administration, solutions of the composition of the invention in either sesame or peanut oil or in aqueous propylene glycol may be employed. The aqueous solutions should be suitably buffered if necessary and the liquid diluent first rendered isotonic. These aqueous solutions are suitable for intravenous injection purposes. The oily solutions are suitable for intraarticular, intramuscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is readily accomplished by standard pharmaceutical techniques well known to those skilled in the an.
Additionally, it is also possible to administer the compositions of the invention topically when treating inflammatory conditions of the skin and this may preferably be done by way of creams, jellies, gels, pastes, ointments and the like, in accordance with standard pharmaceutical practice.
The activity of the compositions of the present invention may be determined by the standard carrageenin-induced rat foot edema test, C.A. Winter et al., Proceedings of the Society for Experimental Biology and Medicine, Vol. 111, p. 544 (1962). Other methods include but are not limited to the formalin paw test, acetic acid writhing test, and models testing adjuvant-induced arthritis.
Claims (5)
1. A pharmaceutical composition for the prevention or treatment of pain or inflammatory diseases which comprises a substance P receptor antagonist and an antiinflammatory or analgesic agent.
2. A composition according to claim 1 wherein said anti-inflammatory or analgesic agent is selected from the group consisting of an opiate agonist, a lipoxygenase inhibitor, a cyclooxygenase inhibitor and an NMDA antagonist.
3. A composition according to claim 1 wherein said anti-inflammatory agent is an inhibitor of nitric oxide or its synthesis.
4. A composition according to claim 1 wherein said anti-inflammatory agent is acetaminophen, aspirin, ibuprofen, piroxicam, naproxen, or indomethacin.
5. A method for the prevention or treatment of pain or inflammatory diseases which comprises administering to a patient in need of such prevention or treatment an effective amount of a substance P receptor antagonist and an antiinflammatory agent.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21332794A | 1994-03-15 | 1994-03-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB9420055D0 GB9420055D0 (en) | 1994-11-16 |
| GB2287404A true GB2287404A (en) | 1995-09-20 |
Family
ID=22794676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9420055A Withdrawn GB2287404A (en) | 1994-03-15 | 1994-10-05 | Antiinflammatory and analgesic compositions |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2287404A (en) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997049402A1 (en) * | 1996-06-27 | 1997-12-31 | Janssen Pharmaceutica N.V. | Sustained release sufentanil compositions |
| US5834480A (en) * | 1997-06-13 | 1998-11-10 | Elkhoury; George F. | Topical application of opioids for treatment of acne and sebaceous gland disorders |
| GB2327041A (en) * | 1997-07-09 | 1999-01-13 | Smithkline Beecham Plc | Topical Analgesic Composition |
| WO1999059635A1 (en) * | 1998-05-21 | 1999-11-25 | Merck Sharp & Dohme Limited | Use of a cox-2 inhibitor and a nk-1 receptor antagonist for treating inflammation |
| EP1007045A4 (en) * | 1994-08-17 | 2000-09-20 | Khoury George F El | Topical application of opioid analgesic drugs such as morphine |
| US6166039A (en) | 1995-09-12 | 2000-12-26 | Regents Of The Univ. Of California | Peripherally active anti-hyperalgesic opiates |
| US6573282B1 (en) | 1995-09-12 | 2003-06-03 | Adolor Corporation | Peripherally active anti-hyperalgesic opiates |
| US6787149B1 (en) | 1996-12-12 | 2004-09-07 | El Khoury And Stein Ltd. | Topical application of opioid analgesic drugs such as morphine |
| WO2004110451A1 (en) * | 2003-06-10 | 2004-12-23 | Janssen Pharmaceutica N.V. | Combinations for opioid-based treatment of pain comprising 1-(1,2-disubstituted piperidinyl)-4-substituted piperazine derivatives |
| WO2004110415A3 (en) * | 2003-06-10 | 2005-02-10 | Janssen Pharmaceutica Nv | Substituted 1, 4-di-piperidin-4-yl-piperazine derivative combined with an opioid analgesic and their use for the treatment of pain and side-effects associated with opioid-based treatments |
| WO2005039545A1 (en) * | 2003-10-29 | 2005-05-06 | Philippe Kriwin | Oral antidepressant formulation comprising acetylsalicylic acid to accelerate onset of action |
| WO2008067610A1 (en) | 2006-12-08 | 2008-06-12 | Adelaide Research & Innovation Pty Ltd | Method for reducing inflammatory responses and inflammation |
| US7662805B2 (en) | 2002-06-10 | 2010-02-16 | Julien Mendlewicz | Oral antidepressant formulation |
| US8604200B2 (en) | 2005-03-08 | 2013-12-10 | Janssen Pharmaceutica N.V. | Diaza-spiro-{4,4}-nonane derivatives as neurokinin (NK1) antagonists |
| US10561627B2 (en) | 2014-12-31 | 2020-02-18 | Eric Morrison | Ibuprofen nanoparticle carriers encapsulated with hermetic surfactant films |
| US10596117B1 (en) | 2014-12-31 | 2020-03-24 | Eric Morrison | Lipoleosomes as carriers for aromatic amide anesthetic compounds |
| US11007161B1 (en) | 2014-12-31 | 2021-05-18 | Eric Morrison | Ibuprofen nanoparticle carriers encapsulated with hermatic surfactant films |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0474561A1 (en) * | 1990-09-05 | 1992-03-11 | Sanofi | Arylalkylamines, process for their preparation and pharmaceutical compositions containing them |
| GB2274777A (en) * | 1993-01-19 | 1994-08-10 | Rhone Poulenc Rorer Sa | Synergistic compositions containing NK1 and NK2 receptor antagonists |
-
1994
- 1994-10-05 GB GB9420055A patent/GB2287404A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0474561A1 (en) * | 1990-09-05 | 1992-03-11 | Sanofi | Arylalkylamines, process for their preparation and pharmaceutical compositions containing them |
| GB2274777A (en) * | 1993-01-19 | 1994-08-10 | Rhone Poulenc Rorer Sa | Synergistic compositions containing NK1 and NK2 receptor antagonists |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1007045A4 (en) * | 1994-08-17 | 2000-09-20 | Khoury George F El | Topical application of opioid analgesic drugs such as morphine |
| US6576650B1 (en) | 1995-09-12 | 2003-06-10 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
| US6573282B1 (en) | 1995-09-12 | 2003-06-03 | Adolor Corporation | Peripherally active anti-hyperalgesic opiates |
| US6166039A (en) | 1995-09-12 | 2000-12-26 | Regents Of The Univ. Of California | Peripherally active anti-hyperalgesic opiates |
| US6113937A (en) * | 1996-06-27 | 2000-09-05 | Janssen Pharmaceutica, N.V. | Sustained release sufentanil compositions |
| WO1997049402A1 (en) * | 1996-06-27 | 1997-12-31 | Janssen Pharmaceutica N.V. | Sustained release sufentanil compositions |
| AU712333B2 (en) * | 1996-06-27 | 1999-11-04 | Janssen Pharmaceutica N.V. | Sustained release sufentanil compositions |
| US6787149B1 (en) | 1996-12-12 | 2004-09-07 | El Khoury And Stein Ltd. | Topical application of opioid analgesic drugs such as morphine |
| US5834480A (en) * | 1997-06-13 | 1998-11-10 | Elkhoury; George F. | Topical application of opioids for treatment of acne and sebaceous gland disorders |
| GB2327041A (en) * | 1997-07-09 | 1999-01-13 | Smithkline Beecham Plc | Topical Analgesic Composition |
| WO1999059635A1 (en) * | 1998-05-21 | 1999-11-25 | Merck Sharp & Dohme Limited | Use of a cox-2 inhibitor and a nk-1 receptor antagonist for treating inflammation |
| AU758983B2 (en) * | 1998-05-21 | 2003-04-03 | Merck Sharp & Dohme Limited | Use of a COX-2 inhibitor and a NK-1 receptor antagonist for treating inflammation |
| US7662805B2 (en) | 2002-06-10 | 2010-02-16 | Julien Mendlewicz | Oral antidepressant formulation |
| WO2004110415A3 (en) * | 2003-06-10 | 2005-02-10 | Janssen Pharmaceutica Nv | Substituted 1, 4-di-piperidin-4-yl-piperazine derivative combined with an opioid analgesic and their use for the treatment of pain and side-effects associated with opioid-based treatments |
| WO2004110451A1 (en) * | 2003-06-10 | 2004-12-23 | Janssen Pharmaceutica N.V. | Combinations for opioid-based treatment of pain comprising 1-(1,2-disubstituted piperidinyl)-4-substituted piperazine derivatives |
| WO2005039545A1 (en) * | 2003-10-29 | 2005-05-06 | Philippe Kriwin | Oral antidepressant formulation comprising acetylsalicylic acid to accelerate onset of action |
| EA011926B1 (en) * | 2003-10-29 | 2009-06-30 | Филипп Кривен | Oral antidepressant formulation comprising acetylsalicylic acid to accelerate onset of action |
| US8604200B2 (en) | 2005-03-08 | 2013-12-10 | Janssen Pharmaceutica N.V. | Diaza-spiro-{4,4}-nonane derivatives as neurokinin (NK1) antagonists |
| WO2008067610A1 (en) | 2006-12-08 | 2008-06-12 | Adelaide Research & Innovation Pty Ltd | Method for reducing inflammatory responses and inflammation |
| US10561627B2 (en) | 2014-12-31 | 2020-02-18 | Eric Morrison | Ibuprofen nanoparticle carriers encapsulated with hermetic surfactant films |
| US10596117B1 (en) | 2014-12-31 | 2020-03-24 | Eric Morrison | Lipoleosomes as carriers for aromatic amide anesthetic compounds |
| US11007161B1 (en) | 2014-12-31 | 2021-05-18 | Eric Morrison | Ibuprofen nanoparticle carriers encapsulated with hermatic surfactant films |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9420055D0 (en) | 1994-11-16 |
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