WO2010120253A1 - Thiocolchicoside and non-steroidal anti-inflammatory drug combinations - Google Patents
Thiocolchicoside and non-steroidal anti-inflammatory drug combinations Download PDFInfo
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- WO2010120253A1 WO2010120253A1 PCT/TR2009/000137 TR2009000137W WO2010120253A1 WO 2010120253 A1 WO2010120253 A1 WO 2010120253A1 TR 2009000137 W TR2009000137 W TR 2009000137W WO 2010120253 A1 WO2010120253 A1 WO 2010120253A1
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- stereoisomers
- salt
- thiocolchicoside
- substantially free
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- SFZJZZCHXLFECJ-QLLBCTQWSA-N CC(NC(CCc(cc(c(OC)c1OC)OC([C@@H](C2=O)O)O[C@H](CO)[C@H]2O)c1C1=CC=C2SC)C1=CC2=O)=O Chemical compound CC(NC(CCc(cc(c(OC)c1OC)OC([C@@H](C2=O)O)O[C@H](CO)[C@H]2O)c1C1=CC=C2SC)C1=CC2=O)=O SFZJZZCHXLFECJ-QLLBCTQWSA-N 0.000 description 1
Classifications
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- 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
- A61K31/5415—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 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- 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
- A61K31/542—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 ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
Definitions
- This invention relates to pharmaceutical compositions and unit dosage forms containing in combination: i. the muscle relaxant thiocolchicoside or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers; ii. a non-steroidal anti-inflammatory drug (NSAID).
- NSAID non-steroidal anti-inflammatory drug
- compositions are useful for the treatment of musculo-skelatal disorders and the treatment of pain and inflammation in mammalian organism, especially for the treatment of low back pain.
- Thiocolchicoside is a glycosulfurated analogue of colchicine and is a well known centrally acting muscle relaxant used in the treatment of musculo-skelatel disorders. Its chemical structure is shown in the Formula 1.
- thiocolchicoside N-[3-( ⁇ -D-glucopyranosyloxy)-l,2- dimethoxy-10-(methylthio)-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide.
- the usual initial dose is 16 mg daily by oral administration in the form of capsules or tablets. It is also used for intramuscular administration in doses up to 8 mg per day or for topical application as cream, ointment, gel or aerosol.
- non-steroidal anti-inflammatory drugs have been utilized in the treatment of pain and inflammation, as well as for a variety of disorders including rheumatoid and osteoarthritis. They vary widely in their chemical structure and biological profiles as analgesics, anti-inflammatory agents and antipyretic agents. They present a superior analgesic and anti-inflammatory activity compared to aspirin and paracetamol but also less side effects like gastrointestinal ulcerations and bleeding experienced with aspirin or hepatic toxicity with large doses of paracetamol.
- Centrally acting skeletal muscle relaxants are generally prescribed either as single agents or as components of combination products.
- Several commercial combinations of a muscle relaxant and aspirin have been approved by the US FDA and are marketed in the
- French patent FR 2725134 Bl (Laboratoire Lederle), filed on 04.10.1994, describes a new combination comprising ibuprofen or a pharmaceutically acceptable salt thereof and thiocolchicoside or a pharmaceutically salt salt thereof in a weight ratio generally comprising between approximately 1:50 and approximately 1 :200 for oral administration in a form of a capsule, a tablet or granules.
- European patent EP 0837684 Bl (Sanofi-Synthelabo), filed on 12.06.1996, describes a new combination comprising a diclofenac salt and thiocolchicoside with at least one pharmaceutically acceptable excipient and provided in a solid form which is stable over time.
- European patent EP 1992333 Al (Sanovel) describes a composition comprising flurbiprofen and an alpha-2 adrenergic receptor agonist or a gamma-aminobutiric acid receptor agonist, in particular tizanidine and thiocolchicoside.
- the physicochemical compatibility of the injectable mixture of thiocolchicoside and other drugs frequently used in association, like anti-inflammatory drugs or vitamins, have been shown for a period of three hours at room temperature in solution (Farmaco.
- the present invention describes new combinations of thiocolchicoside and NSAID in unit dosage form which is stable over time.
- the present invention relates to a combination of the muscle relaxant thiocolchicoside and its pharmaceutically acceptable salts with at least one non-steroidal antiinflammatory drug and at least one pharmaceutically acceptable non-toxic carrier adapted for unit dose administration.
- the muscle relaxant for use in the pharmaceutical compositions and methods of use of the present invention is thiocolchicoside.
- the invention includes any pharmaceutically acceptable salt of thiocolchicoside and any therapeutically active stereoisomer of thiocolchicoside, substantially free of its other stereoisomers.
- the amount of thiocolchicoside useful in the practice of the present invention may vary from 4 mg to 16 mg depending on the mode of administration.
- the preferred amount of thiocolchicoside is selected from a range 4 to 8 mg per unit for parenteral administration.
- the preferred amount of thiocolchicoside is selected from a range 8 to 16 mg per unit
- the NSAID for use in the pharmaceutical compositions and methods of use of the present invention may be chosen from the group consisting of, but not limited to, the oxicams, the fenamic acid derivatives, the acetic acid derivatives, the propionic acid derivatives, the coxibs and other NSAIDs. They include all their pharmaceutically acceptable salts of thereof or therapeutically active stereoisomers therof, substantially free of their other stereoisomers. These compounds are well known to those skilled in art and described in various literature reference sources like the Merck Index for their chemical structures, pharmacological activities, side effects, normal dosage ranges, etc.
- the preferred oxicams for use in the present invention include, but are not limited to, lornoxicam, tenoxicam, meloxicam and piroxicam.
- the preferred fenamic acid derivatives for use in the present invention include, but are not limited to, mefenamic acid and etofenamate.
- the preferred acetic acid derivatives for use in the present invention include, but are not limited to, etodolac, acemetacin and indometacin.
- the preferred propionic acid derivatives for use in the present invention include, but are not limited to, tiaprofenic acid, naproxen and oxaprozin.
- the preferred coxibs for use in the present invention include, but are not limited to, celecoxib, rofecoxib, lumiracoxib and valdecoxib.
- the preferred other NSAID' s for use in the present invention include, but are not limited to, nimesulide.
- the present pharmaceutical compositions may be used for oral, buccal, ocular, otic, dermal, rectal, epidermal, topical, transdermal, implantal, mucosal, parenteral, sublingal, nasal, or pulmonary administration in the form of gel, cream, ointment, tablet, capsule, bead, granule, liquid, suspension, syrup, powder, injectable suspension, injectable powder and injectable liquid.
- the present pharmaceutical compositions may be administrated in a mixture with suitable non-toxic pharmaceutical carriers or excipients suitably selected with respect to the intented route of administration and conventional pharmaceutical practices known by the people skilled in the art.
- the active substances may be combined with any oral non-toxic pharmaceutically acceptable inert carrier such as lactose, starch, pregelatinized starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol and the like.
- suitable binders, lubricants, disintegrating agents and flavoring, sweetening or coloring agents can also be added.
- suitable binders include starch, pregelatinized starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums, sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, etc.
- Suitable lubricants / glidants include magnesium stearate, talc, boric acid, sodium benzoate, sodium acetate, sodium chloride, etc.
- suitable disintegrators include starch, methylcellulose, agar, etc.
- suitable coating agents include hydroxypropylmethyl cellulose as film former, PEG 400 as plasticizer, titanium dioxide and iron oxide as colouring agent.
- the invention may be formulated in the form of a extended, modified or extended release tablet or capsule to provide the control of the release of thiocolchicoside and / or the NSAID in order to optimize the therapeutic effects and minimize the undesirable side effects.
- the present invention may be an injectable dosage unit for intravenous, intramuscular or subcutaneous administration formulated as aqueous or non-aqueous solution, suspension or powder for injection with the appropriate non-toxic pharmaceutically acceptable excipients.
- the present pharmaceutical compositions are useful for the treatment of musculo- skelatal disorders and the treatment of pain and inflammation in mammalian organism, especially for the treatment of low back pain. They can be administrated in unit dose 1 or 2 times per day.
- the following examples illustrate the compositions of the present invention and as such are to be considered as limiting the invention set forth in the claims appended hereto.
- Example 1 Powder for injection
- Example 2 Coated tablet
- the compounds are mixed by conventional techniques then pressed into tablet forms and coated.
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Abstract
This invention relates to pharmaceutical compositions and unit dosage forms containing in combination: the muscle relaxant thiocolchicoside or a salt of thereof or any therapeutically active stereoisomer thereof, substantially free of its other stereoisomers; a non-steroidal anti-inflammatory drug (NSAID).
Description
Thiocolchicoside and non-steroidal anti-inflammatory drug combinations
This invention relates to pharmaceutical compositions and unit dosage forms containing in combination: i. the muscle relaxant thiocolchicoside or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers; ii. a non-steroidal anti-inflammatory drug (NSAID).
The pharmaceutical compositions are useful for the treatment of musculo-skelatal disorders and the treatment of pain and inflammation in mammalian organism, especially for the treatment of low back pain.
Thiocolchicoside is a glycosulfurated analogue of colchicine and is a well known centrally acting muscle relaxant used in the treatment of musculo-skelatel disorders. Its chemical structure is shown in the Formula 1.
Formula 1
The chemical name of thiocolchicoside is N-[3-(β-D-glucopyranosyloxy)-l,2- dimethoxy-10-(methylthio)-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide. The usual initial dose is 16 mg daily by oral administration in the form of capsules or tablets. It is also used for intramuscular administration in doses up to 8 mg per day or for topical application as cream, ointment, gel or aerosol.
The non-steroidal anti-inflammatory drugs have been utilized in the treatment of pain and inflammation, as well as for a variety of disorders including rheumatoid and osteoarthritis. They vary widely in their chemical structure and biological profiles as analgesics, anti-inflammatory agents and antipyretic agents. They present a superior analgesic and anti-inflammatory activity compared to aspirin and paracetamol but also
less side effects like gastrointestinal ulcerations and bleeding experienced with aspirin or hepatic toxicity with large doses of paracetamol.
Centrally acting skeletal muscle relaxants are generally prescribed either as single agents or as components of combination products. Several commercial combinations of a muscle relaxant and aspirin have been approved by the US FDA and are marketed in the
USA like carisoprodol + aspirin (Soma Compound, Meda Pharms), carisoprodol + aspirin + codeine (Soma Compound W/ Codeine), methocarbamol + aspirin
(Methocarbarbamol and Aspirin, Ivax Pharms) and orphenadrine + aspirin + caffeine
(Norgesic Forte, Graceway). However, few combinations of the muscle relaxant thiocolchicoside with NSAID have been described in the past and none of the descriptions includes the combinations disclosed in the present invention.
French patent FR 2725134 Bl (Laboratoire Lederle), filed on 04.10.1994, describes a new combination comprising ibuprofen or a pharmaceutically acceptable salt thereof and thiocolchicoside or a pharmaceutically salt salt thereof in a weight ratio generally comprising between approximately 1:50 and approximately 1 :200 for oral administration in a form of a capsule, a tablet or granules.
European patent EP 0837684 Bl (Sanofi-Synthelabo), filed on 12.06.1996, describes a new combination comprising a diclofenac salt and thiocolchicoside with at least one pharmaceutically acceptable excipient and provided in a solid form which is stable over time.
European patent EP 1992333 Al (Sanovel) describes a composition comprising flurbiprofen and an alpha-2 adrenergic receptor agonist or a gamma-aminobutiric acid receptor agonist, in particular tizanidine and thiocolchicoside. The physicochemical compatibility of the injectable mixture of thiocolchicoside and other drugs frequently used in association, like anti-inflammatory drugs or vitamins, have been shown for a period of three hours at room temperature in solution (Farmaco.
2002 Nov; 57(11):925-30).
The addition of thiocolchicoside to NSAID standard treatment has shown more effective results for the treatment of low back pain than the NSAID alone. In addition, the
combination was well tolerated and produced no more adverse reactions than the NSAID alone (J Orthopaed Traumatol (2002) 3-103-108).
The present invention describes new combinations of thiocolchicoside and NSAID in unit dosage form which is stable over time. The present invention relates to a combination of the muscle relaxant thiocolchicoside and its pharmaceutically acceptable salts with at least one non-steroidal antiinflammatory drug and at least one pharmaceutically acceptable non-toxic carrier adapted for unit dose administration. The muscle relaxant for use in the pharmaceutical compositions and methods of use of the present invention is thiocolchicoside. The invention includes any pharmaceutically acceptable salt of thiocolchicoside and any therapeutically active stereoisomer of thiocolchicoside, substantially free of its other stereoisomers. The amount of thiocolchicoside useful in the practice of the present invention may vary from 4 mg to 16 mg depending on the mode of administration. The preferred amount of thiocolchicoside is selected from a range 4 to 8 mg per unit for parenteral administration. The preferred amount of thiocolchicoside is selected from a range 8 to 16 mg per unit for oral administration.
The NSAID for use in the pharmaceutical compositions and methods of use of the present invention may be chosen from the group consisting of, but not limited to, the oxicams, the fenamic acid derivatives, the acetic acid derivatives, the propionic acid derivatives, the coxibs and other NSAIDs. They include all their pharmaceutically acceptable salts of thereof or therapeutically active stereoisomers therof, substantially free of their other stereoisomers. These compounds are well known to those skilled in art and described in various literature reference sources like the Merck Index for their chemical structures, pharmacological activities, side effects, normal dosage ranges, etc. The preferred oxicams for use in the present invention include, but are not limited to, lornoxicam, tenoxicam, meloxicam and piroxicam.
The preferred fenamic acid derivatives for use in the present invention include, but are not limited to, mefenamic acid and etofenamate. The preferred acetic acid derivatives for use in the present invention include, but are not limited to, etodolac, acemetacin and indometacin.
The preferred propionic acid derivatives for use in the present invention include, but are not limited to, tiaprofenic acid, naproxen and oxaprozin.
The preferred coxibs for use in the present invention include, but are not limited to, celecoxib, rofecoxib, lumiracoxib and valdecoxib.
The preferred other NSAID' s for use in the present invention include, but are not limited to, nimesulide.
The preferred unit dose for the preferred compounds mentionned hereinabove are listed in Table 1.
Compound Preferred unit dose
Acemetacin 30 - 180 mg
Etodolac 300 - 1200 mg
Etofenamate 500 - 1000 mg
Indometacin 25 - 200 mg
Lornoxicam 4 - 16 mg
Mefenamic acid 250 - 1500 mg
Meloxicam 3,75 - 15 mg
Naproxen 250 - 1000 mg
Nimesulide 50 - 200 mg
Oxaprozin 300 - 1200 mg
Piroxicam 5 - 40 mg
Tenoxicam 10 - 40 mg
Thiocolchicoside 4 - 16 mg
Tiaprofenic acid 200 - 600 mg Table 1
The present pharmaceutical compositions may be used for oral, buccal, ocular, otic, dermal, rectal, epidermal, topical, transdermal, implantal, mucosal, parenteral, sublingal, nasal, or pulmonary administration in the form of gel, cream, ointment, tablet, capsule, bead, granule, liquid, suspension, syrup, powder, injectable suspension, injectable powder and injectable liquid.
The present pharmaceutical compositions may be administrated in a mixture with suitable non-toxic pharmaceutical carriers or excipients suitably selected with respect to the intented route of administration and conventional pharmaceutical practices known by the people skilled in the art. For oral administration in a form of a tablet or a capsule, the active substances may be combined with any oral non-toxic pharmaceutically acceptable inert carrier such as lactose, starch, pregelatinized starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol and the like. When desired or necessary, suitable binders, lubricants, disintegrating agents and flavoring, sweetening or coloring agents can also be added. Examples of suitable binders include starch, pregelatinized starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums, sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, etc. Examples of suitable lubricants / glidants include magnesium stearate, talc, boric acid, sodium benzoate, sodium acetate, sodium chloride, etc. Examples of suitable disintegrators include starch, methylcellulose, agar, etc. Examples of suitable coating agents include hydroxypropylmethyl cellulose as film former, PEG 400 as plasticizer, titanium dioxide and iron oxide as colouring agent. Optionnally the invention may be formulated in the form of a extended, modified or extended release tablet or capsule to provide the control of the release of thiocolchicoside and / or the NSAID in order to optimize the therapeutic effects and minimize the undesirable side effects.
Similarly, the present invention may be an injectable dosage unit for intravenous, intramuscular or subcutaneous administration formulated as aqueous or non-aqueous solution, suspension or powder for injection with the appropriate non-toxic pharmaceutically acceptable excipients. The present pharmaceutical compositions are useful for the treatment of musculo- skelatal disorders and the treatment of pain and inflammation in mammalian organism, especially for the treatment of low back pain. They can be administrated in unit dose 1 or 2 times per day. The following examples illustrate the compositions of the present invention and as such are to be considered as limiting the invention set forth in the claims appended hereto.
Example 1 : Powder for injection
Weight per unit dose
Tenoxicam 10,0 mg
Thiocolchicoside 4,0 mg
Mannitol 50,0 mg
Trometamol 1,5 mg
NaOH 1,6 mg
Na metabisulfite 2,0 mg
Na EDTA 0,2 mg
The compounds are dissolved and mixed in water for injection. The obtained solution is filtered at 0,2 μm, filled in vials and lyophilized. Example 2: Coated tablet
Weight per unit dose
Core:
Tenoxicam 10,0 mg
Thiocolchicoside 8,0 mg
Lactose Monohydrate 90,0 mg
Starch 86,0 mg
Talc 3,0 mg
Magnesium Stearate 1,0 mg
Coating:
Hydroxypropylmethyl cellulose 2,9 mg
Titanium Dioxide 1,8 mg
PEG 400 0,3 mg
Iron Oxide 0,6 mg
The compounds are mixed by conventional techniques then pressed into tablet forms and coated.
Claims
1. A pharmaceutical composition for use in the treatment of muscloskeletal disorders and the treatment of pain and inflammation in mammalian organism and adapted for unit administration comprising a pharmaceutically effective amount of: a) one muscle relaxant; b) at least one non-steroidal anti-inflammatory drug; c) at least one pharmaceutically acceptable non-toxic carrier.
2. The pharmaceutical composition of claim 1 where the said muscle relaxant is thiocolchicoside, or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
3. The pharmaceutical composition of claim 1 where the said non-steroidal antiinflammatory agent is selected from the group consisting of oxicams, fenamic acid derivatives, acetic acid derivatives, propionic acid derivatives, coxibs and other non-steroidal antiinflammatories.
4. The pharmaceutical composition of claim 3 where the said oxicam is lornoxicam or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
5. The pharmaceutical composition of claim 3 where the said oxicam is tenoxicam or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
6. The pharmaceutical composition of claim 3 where the said oxicam is meloxicam or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
7. The pharmaceutical composition of claim 3 where the said oxicam is piroxicam or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
8. The pharmaceutical composition of claim 3 where the said fenamic acid derivative is mefenamic acid or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
9. The pharmaceutical composition of claim 3 where the said fenamic acid derivative is etofenamate or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
10. The pharmaceutical composition of claim 3 where the said acetic acid derivative is etodolac or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
1 1. The pharmaceutical composition of claim 3 where the said acetic acid derivative is acemetacin or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
12. The pharmaceutical composition of claim 3 where the said acetic acid derivative is indometacin or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
13. The pharmaceutical composition of claim 3 where the said propionic acid derivative is tiaprofenic acid or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
14. The pharmaceutical composition of claim 3 where the said propionic acid derivative is naproxen or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
15. The pharmaceutical composition of claim 3 where the said propionic acid derivative is oxaprozin or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
16. The pharmaceutical composition of claim 3 where the said coxib is celecoxib or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
17. The pharmaceutical composition of claim 3 where the said coxib is rofecoxib or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
18. The pharmaceutical composition of claim 3 where the said coxib is lumiracoxib or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
19. The pharmaceutical composition of claim 1 where the said coxib is valdecoxib or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.,
20. The pharmaceutical composition of claim 3 where the said other non-steroidal anti- inflammatory is nimesulide or a salt of thereof or any therapeutically active stereoisomer therof, substantially free of its other stereoisomers.
21. The pharmaceutical composition of claim 1, wherein the weight ratio of muscle relaxant to non-steroidal anti-inflammatory agent varies from 1 :300 to 16:3,75.
22. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 4 mg to 16 mg of lornoxicam.
23. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 10 mg to 40 mg of tenoxicam.
24. The pharmaceutical composition as defined by claim 1 , comprising from about 4 mg to 16 mg of thiocolchicoside and from about 3,75 mg to 15 mg of meloxicam.
25. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 5 mg to 40 mg of piroxicam.
26. The pharmaceutical composition as defined by claim 1 , comprising from about 4 mg to 16 mg of thiocolchicoside and from about 250 mg to 1500 mg of mefenamic acid.
27. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 500 mg to 1000 mg of etofenamate.
28. The pharmaceutical composition as defined by claim 1 , comprising from about 4 mg to 16 mg of thiocolchicoside and from about 300 mg to 1200 mg of etodolac.
29. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 30 mg to 180 mg of acemetacin.
30. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 25 mg to 200 mg of indometacin.
31. The pharmaceutical composition as defined by claim 1 , comprising from about 4 mg to 16 mg of thiocolchicoside and from about 200 mg to 600 mg of tiaprofenic acid.
32. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 250 mg to 1000 mg of naproxen.
33. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 300 mg to 1200 mg of oxaprozin.
34. The pharmaceutical composition as defined by claim 1, comprising from about 4 mg to 16 mg of thiocolchicoside and from about 50 mg to 200 mg of nimesulide.
35. The pharmaceutical dosage form of claim 1, wherein the pharmaceutical dosage form is adapted for oral, buccal, ocular, otic, dermal, rectal, epidermal, topical, transdermal, implant, mucosal, parenteral, sublingal, nasal, or pulmonary delivery.
36. The pharmaceutical dosage form of claim 1, wherein the pharmaceutical dosage form is used for oral administration.
37. The pharmaceutical dosage form of claim 1, wherein the pharmaceutical dosage form is used for parenteral administration.
38. The pharmaceutical dosage form of claim 1, wherein the dosage form is selected from the group consisting of a gel, cream, ointment, tablet, capsule, bead, pellet, granule, liquid, suspension, syrup, powder, injectable suspension, injectable powder and injectable liquid.
39. The pharmaceutical composition of claim 1 wherein the composition is administrated in the form of a tablet.
40. The pharmaceutical composition of claim 1 wherein the composition is administrated in the form of a capsule.
41. The pharmaceutical composition of claim 1 wherein the composition is administrated in the form of a solution for injection.
42. The pharmaceutical composition of claim 1 wherein the composition is administrated in the form of a powder for injection.
43. The pharmaceutical composition of claim 1 wherein the composition is administrated in the form of a suspension for injection.
44. The pharmaceutical dosage form of claim 1 , wherein the dosage form indepently provides a controlled, delayed, sustained, immediate, timed, slow or rapid release of each of the muscle relaxant and the non-steroidal anti-inflammatory agent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2009/03036 | 2009-04-17 | ||
| TR2009/03036A TR200903036A2 (en) | 2009-04-17 | 2009-04-17 | Combinations of thiocolchicoside and non-steroidal anti-inflammatory drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2010120253A1 true WO2010120253A1 (en) | 2010-10-21 |
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| Application Number | Title | Priority Date | Filing Date |
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| PCT/TR2009/000137 WO2010120253A1 (en) | 2009-04-17 | 2009-11-04 | Thiocolchicoside and non-steroidal anti-inflammatory drug combinations |
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| TR (1) | TR200903036A2 (en) |
| WO (1) | WO2010120253A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012173581A1 (en) * | 2011-03-21 | 2012-12-20 | Ak Kimya Ithalat-Ihracat Ve Sanayii A.S. | Thiocolchicoside, etodolac and famotidine combinations |
| WO2014125085A1 (en) * | 2013-02-15 | 2014-08-21 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Oral pharmaceutical formulations comprising nimesulide and thiocolchicoside |
| EP2977045A1 (en) * | 2014-07-21 | 2016-01-27 | Sanovel Ilac Sanayi ve Ticaret A.S. | Zaltoprofen and muscle relaxant combinations |
| WO2016089966A1 (en) * | 2014-12-02 | 2016-06-09 | Rarecyte, Inc. | Solution and method for adhering suspension components to a substrate |
| EP3173077A1 (en) * | 2015-11-30 | 2017-05-31 | Sanovel Ilac Sanayi ve Ticaret A.S. | Tablet formulations of nimesulide and thiocolchicoside |
| EP3932397A4 (en) * | 2019-03-01 | 2022-12-07 | Eurofarma Laboratórios S.A. | Non-steroidal anti-inflammatory lyophilized pharmaceutical composition |
Citations (1)
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| WO2006097149A1 (en) * | 2005-03-17 | 2006-09-21 | Pharmafilm S.R.L. | An aqueous polymeric system for pressure sensitive adhesive matrix preparation |
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- 2009-11-04 WO PCT/TR2009/000137 patent/WO2010120253A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2006097149A1 (en) * | 2005-03-17 | 2006-09-21 | Pharmafilm S.R.L. | An aqueous polymeric system for pressure sensitive adhesive matrix preparation |
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| AKSOY C ET AL: "Low back pain: results of an open clinical trial comparing the standard treatment alone to the combination of standard treatment and thiocolchicoside", JOURNAL OF ORTHOPAEDICS AND TRAUMATOLOGY, SPRINGER ITALIA, IT, vol. 3, 1 January 2002 (2002-01-01), pages 103 - 108, XP003024887, ISSN: 1590-9921 * |
| ANACARDIO R ET AL: "Physicochemical compatibility between thiocolchicoside injections (Miotens(R)) and pharmaceutical products frequently used for combined therapy", FARMACO, SOCIETA CHIMICA ITALIANA, PAVIA, IT, vol. 57, no. 11, 1 November 2002 (2002-11-01), pages 925 - 930, XP008111399, ISSN: 0014-827X * |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012173581A1 (en) * | 2011-03-21 | 2012-12-20 | Ak Kimya Ithalat-Ihracat Ve Sanayii A.S. | Thiocolchicoside, etodolac and famotidine combinations |
| WO2014125085A1 (en) * | 2013-02-15 | 2014-08-21 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Oral pharmaceutical formulations comprising nimesulide and thiocolchicoside |
| EP2977045A1 (en) * | 2014-07-21 | 2016-01-27 | Sanovel Ilac Sanayi ve Ticaret A.S. | Zaltoprofen and muscle relaxant combinations |
| WO2016012398A1 (en) * | 2014-07-21 | 2016-01-28 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Zaltoprofen and muscle relaxant combinations |
| WO2016089966A1 (en) * | 2014-12-02 | 2016-06-09 | Rarecyte, Inc. | Solution and method for adhering suspension components to a substrate |
| EP3173077A1 (en) * | 2015-11-30 | 2017-05-31 | Sanovel Ilac Sanayi ve Ticaret A.S. | Tablet formulations of nimesulide and thiocolchicoside |
| WO2017093212A1 (en) * | 2015-11-30 | 2017-06-08 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Tablet formulations of nimesulide and thiocolchicoside |
| EP3932397A4 (en) * | 2019-03-01 | 2022-12-07 | Eurofarma Laboratórios S.A. | Non-steroidal anti-inflammatory lyophilized pharmaceutical composition |
Also Published As
| Publication number | Publication date |
|---|---|
| TR200903036A2 (en) | 2010-06-21 |
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