EP2956125A1 - Oral pharmaceutical formulations comprising nimesulide and thiocolchicoside - Google Patents

Oral pharmaceutical formulations comprising nimesulide and thiocolchicoside

Info

Publication number
EP2956125A1
EP2956125A1 EP14705127.0A EP14705127A EP2956125A1 EP 2956125 A1 EP2956125 A1 EP 2956125A1 EP 14705127 A EP14705127 A EP 14705127A EP 2956125 A1 EP2956125 A1 EP 2956125A1
Authority
EP
European Patent Office
Prior art keywords
formulation according
tablet formulation
sodium
thiocolchicoside
nimesulide
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.)
Withdrawn
Application number
EP14705127.0A
Other languages
German (de)
French (fr)
Inventor
Ali TÜRKYILMAZ
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanovel Ilac Sanayi ve Ticaret AS
Original Assignee
Sanovel Ilac Sanayi ve Ticaret AS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sanovel Ilac Sanayi ve Ticaret AS filed Critical Sanovel Ilac Sanayi ve Ticaret AS
Publication of EP2956125A1 publication Critical patent/EP2956125A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer

Definitions

  • the patent EP0853476B1 discloses a pharmaceutical preparation comprising as active agent nimesulide or a pharmaceutically acceptable salt thereof, characterized in that the preparation's base contains one phospholipid and at least one substance with acid reaction, specifically an acid.
  • the layers comprising nimesulide and thiocolchicoside are separated by an inert layer so as to give a multilayer tablet formulation.
  • an inert layer By virtue of using a cellulosic polymer in the inert layer, the efficient and safe plasma levels of both active agents are achieved rapidly. Thus, the absorption and the bioavailability of the pharmaceutical formulation are increased as well.
  • the cellulosic polymers used are preferably hydroxypropyl cellulose and microcrystalline cellulose.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention relates to a novel pharmaceutical combination comprising nimesulide or a pharmaceutically acceptable salt thereof and thiocolchicoside or a pharmaceutically acceptable salt thereof with anti-inflammatory, analgesic and myorelaxant effects. The present invention particularly relates to a pharmaceutical combination in the form of a multilayer oral tablet comprising nimesulide and thiocolchicoside with anti-inflammatory, analgesic and myorelaxant effects.

Description

Description
ORAL PHARMACEUTICAL FORMULATIONS COMPRISING NIMESULIDE AND
THIOCOLCHICOSIDE
Technical Field
The present invention relates to a novel pharmaceutical combination comprising nimesulide or a pharmaceutically acceptable salt thereof and thiocolchicoside or a pharmaceutically acceptable salt thereof with anti-inflammatory, analgesic and myorelaxant effects.
The present invention more particularly relates to a pharmaceutical combination in the form of a multilayer oral tablet comprising nimesulide and thiocolchicoside with antiinflammatory, analgesic and myorelaxant effects.
Background of Invention
Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) molecule with the chemical structure illustrated in Formula 1 below.
Nimesulide selectively inhibits the cyclooxygenase-2 (COX-2) enzyme. It has antipyretic, analgesic, and anti-inflammatory effects. It is used in osteoarthritis and extraarticular rheumatic diseases, post-traumatic and post-operative inflammations and painful symptoms, high fever, and in dysmenorrhea!.
Thiocolchicoside is a myorelaxant with the structure illustrated in Formula 2 below.
Formula 2: Thiocolchicoside
Thiocolchicoside is a semi-synthetic sulfur salt, obtained from colchicoside, a natural glycoside found in Anatolian Colchicum Autumnale (Autumn crocuses). This natural glycoside has muscle relaxant, anti-inflammatory and analgesic effects. Thiocolchicoside exerts the myorelaxant effect by activating the gamma-aminobutyric acid (GABA) and glycine receptors at the spinal level. Furthermore, glycinomimetic effects of thiocolchicoside are seen in the nerve system at varying levels. It does not have a curarizing effect. It does not give rise to motor plaque paralysis, and no inhalation-related problems are encountered. It does not have effects on the cardiovascular system either. Muscle relaxants also reduce the muscle tonus and are used in treating muscle spasms and contractures. Muscle spasm is one of the main factors held responsible for chronic pains; in addition to rheumatic inflammatory and degenerative orthopedic pathologies, it defines various pathologies of the locomotor system as well; when it affects the joints, it does not cause pain only, but it leads to stiffness that reduces the mobility and flexibility of joints at the affected site.
Muscle contractures also characterizes various pathologies of the locomotor system, and is one of the main causes, which is deemed responsible for the persistency of pain associated with such pathologies. Muscle relaxants are used in neuromuscular and muscle-skeleton system injuries. There are two main types of muscle relaxants: centrally-acting muscle relaxants and directly- acting muscle relaxants. Centrally-acting muscle relaxants typically act on the central nervous system (CNS) in a selective manner and are primarily used for alleviating painful muscle spasms and the strains occurring during muscle-skeleton system and neuromuscular damages. The action mechanisms thereof are associated with the causes of the CNS-suppressing activities.
Accordingly, muscle relaxants and antispasmodic molecules constitute a subject matter which is still clinically significant.
Recently, it has been reported that the activity of thiocolchicoside was based on its capability of interacting with strychnine-sensitive glycine receptors, and therefore compounds with glycinomimetic effects have been introduced for use in rheumatologic- orthopedic fields as muscle relaxants.
Muscle relaxants are used alone or together with customary analgesics in treating pain. In fact, a pharmaceutical combination may give complex or unforeseeable outcomes; but so far, nimesulide has never been used together with thiocolchicoside in a pharmaceutical combination for treating inflammatory, pain, and muscle-skeletal system diseases. Researching the patent literature may result in various patents which relate to nimesulide and thiocolchicoside.
The patent EP0853476B1 (Errekappa Euroterapici SpA) discloses a pharmaceutical preparation comprising as active agent nimesulide or a pharmaceutically acceptable salt thereof, characterized in that the preparation's base contains one phospholipid and at least one substance with acid reaction, specifically an acid.
The patent FR 2 725 134 B1 discloses a novel pharmaceutical composition comprising ibuprofen or a pharmaceutically acceptable salt thereof and thiocolchicoside or a pharmaceutically acceptable salt thereof in a ratio ranging from around 1 :50 to around 1 :200. According to that invention, said pharmaceutical composition is useful in treating painful muscle syndromes and more specifically in treating lumbagos. The patent EP 0 837 684 B1 discloses a pharmaceutical composition comprising, in solid form, a diclofenac salt and thiocolchicoside, combined with at least one pharmaceutically acceptable carrier, for use in therapy. According to that invention, the muscle relaxant drug used in combination with flurbiprofen is metocarbamol and this combination is particularly used in treating influenza and common cold symptoms involving sore throat.
So far, no multilayer tablet formulation comprising a combination of thiocolchicoside and nimesulide has been made. Even if muscle relaxants and non-steroidal inflammatory drugs have been used together in practice, this requires the patients to carry more than one drug and causes inconvenience in terms of practicality.
Despite the fact that at least an additive therapeutic effect is expected for the drugs used in the same therapeutic field or even for the treatment of the same indication, it is well known that these drugs cannot a priori be combined in all cases. The scientific literature is full of examples showing that the compounds from different classes used for treating the same indication cannot always be combined in reliable and efficient dosage forms and therefore may result in incompatible drug combinations. The causes of this unexpected incompatibility are diverse; the typically observed outcomes, however, include the increases in the side effects of different drug combinations, undesired drug interactions, and formation of new side effects. More specifically, drug combinations are available in the field of analgesia, which are contraindicated due to some or all of the causes very similar to those described above. The basic difficulties encountered when two or more molecules are combined in the same pharmaceutical dosage form are (a) ensuring compatibility between different active agents and/or among the active agents and the excipients used, (b) providing therapeutic compatibility between the active agents, taking into account the pharmacokinetic and/or biopharmaceutical properties such as the posology of the respective combination to obtain efficient and reliable plasma levels of both active agents.
Conventional analgesic and myorelaxant treatments typically comprise administrating one or more different analgesic and muscle relaxant drug(s) in the form of a pharmaceutical composition. However, in terms of safety and reduced side effects, the combinations of analgesic drugs and muscle relaxant drugs are not always more convenient than immediate release formulations as to the reduced dosage schedule in terms of higher compatibility and higher patient compliance. Therefore, there is a need to develop a formulation having an immediate release layer comprising nimesulide and an immediate release layer or a controlled release layer comprising thiocolchicoside for providing an efficient treatment of pain, spasticity, inflammatory symptoms and painful muscle spasms, as well as an improved side effect profile and increased patient compliance.
Description of Figures
Figure 1 illustrates an oral solid multilayer tablet formulation having i) a first layer (a) comprising a first active agent, ii) a second layer (b) comprising a second active agent, and iii) a barrier layer (c) separating these two layers from each other.
Detailed Description of Invention
The present invention relates to an easily administrable nimesulide and thiocolchicoside combination, eliminating all aforesaid problems and brining additional advantages to the relevant prior art.
Accordingly, the main object of the present invention is to obtain a multilayer tablet formulation comprising a stable and well-soluble combination of nimesulide and thiocolchicoside with anti-inflammatory, analgesic, and myorelaxant effects.
The layer comprising nimesulide and the layer comprising thiocolchicoside are separated using an inert layer such that the incompatibility of these agents is eliminated and efficient and safe plasma levels are obtained. While the layer (a) comprising nimesulide provides immediate release, the layer (b) comprising thiocolchicoside provides either immediate release or controlled release. These two layers are separated using an inert layer (c). The present invention preferably comprises nimesulide in the immediate release layer and thiocolchicoside in the immediate release layer.
As stated above, the layers comprising nimesulide and thiocolchicoside are separated by an inert layer so as to give a multilayer tablet formulation. By virtue of using a cellulosic polymer in the inert layer, the efficient and safe plasma levels of both active agents are achieved rapidly. Thus, the absorption and the bioavailability of the pharmaceutical formulation are increased as well. The cellulosic polymers used are preferably hydroxypropyl cellulose and microcrystalline cellulose.
Another object of the present invention is to obtain a formulation which dissolves well in the gastrointestinal fluid. It was surprisingly found that the ratio of the disintegrants used in the active agent-comprising layers has a substantial influence on the release properties of the tablet. The amount of the disintegrant is 1 .0 to 30.0%, preferably 2.0 to 20.0% in the nimesulide-comprising layer and the amount of the disintegrant is 3.0 to 35.0%, preferably 5.0 to 25.0% in the thiocolchicoside-comprising layer; thus the different ratios of the disintegrant in the different layers provide well dissolving the multilayer tablet formulation in the gastrointestinal fluid and improve the absorption thereof. While higher amounts can give rise to negative effects on the mechanical strength of the formulation, lower amounts may worsen the disintegration time. Suitable disintegrants for use in the formulation according to the present invention are alginic acid and alginates, ion-exchange resins, magnesium aluminum silicate, sodium dodecyl sulfate, sodium carboxymethyl cellulose, croscarmellose sodium, cross linked polyvinylpyrrolidone, carboxymethylcellulose calcium, docusate sodium, guar gum, corn starch, polacrilin potassium, poloxamer, povidone, sodium alginate, sodium glycine carbonate, sodium lauryl sulfate, sodium starch glycolate, or the mixtures thereof.
The pharmaceutical compositions according to the present invention may further comprise one or more pharmaceutically acceptable excipient(s). The pharmaceutically acceptable excipients comprise at least one selected from the group consisting of fillers, binders, lubricants and glidants, flavoring agents, sweeteners and coloring agents.
Suitable fillers for use in the formulation according to the present invention are mannitol, spray-dried mannitol; polysaccharides such as microcrystalline cellulose; dibasic calcium phosphate dihydrate, lactose, sugars, sorbitol, lactose monohydrate; a mixture of microcrystalline cellulose and guar gum (Avicel CE-15); a mixture of mannitol, polyplasdone and syolid (Pharmaburst); a mixture of mannitol, crospovidone and polyvinyl acetate (Ludiflash); inorganic salts such as isomalt, sucrose, calcium salts, or the mixtures thereof. The amount of the filler is 2.0 to 90.0%, preferably 10.0 to 85.0%, and more preferably 15.0 to 80.0% of the total weight of the tablet.
Suitable binders for use in the formulation according to the present invention are natural gums, starch, gelatin, polyvinylpyrrolidone, polymethacrylates; collagen, proteins such as gelatin; semisynthetic polymers such as agar, alginate, sodium alginate, pectin, starch, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose; synthetic polymers such as carbomer, poloxamer, polyacrylamide, polyvinyl alcohol; inorganic substances such as aluminum hydroxide, bentonite, laponite; starch mucilage, acacia mucilage, polydextrose, polyethylene oxide, or the mixtures thereof. The amount of the binder is 0.001 to 55.0%, preferably 0.1 to 30.0% of the total weight of the tablet.
Suitable lubricants and glidants for use in the formulation according to the present invention are sodium stearyl fumarate, magnesium stearate, polyethylene glycol, colloidal silicon dioxide, stearic acid, talk, metal stearates, boric acid, sodium chloride benzoate and acetate, sodium or magnesium lauryl sulfate, or the mixtures thereof. The total amount of the lubricant and the glidant is 0.01 to 20.0%, preferably 0.1 to 10.0% of the total weight of the tablet.
Suitable sweeteners for use in the formulation according to the present invention are sucralose, acesulfame-K, aspartame, saccharine or saccharine sodium and calcium salts, sodium cyclamate, sucrose, fructose, glucose, sorbitol, or the mixtures thereof. The amount of the sweetener is 0.01 to 15.0% of the total weight of the tablet.
Suitable flavoring agents for use in the formulation according to the present invention are fruit aromas such as orange, banana, strawberry, cherry, wild cherry, lemon; cardamom, anis, mint, menthol, vanillin, and ethyl vanillin, and other similar aromas, or the mixtures thereof. The amount of the flavoring agent is 0.01 to 10.0% of the total weight of the tablet.
The present invention is used for treating osteoarthritis, pain associated with tissue trauma following osteoarthritis surgery, psoriatic arthritis, rheumatoid arthritis, myalgia, bone pain, arthralgia, muscle spasms, soft tissue traumas, lumbago, back pain, sciatica and torticollis.
The present invention will be further described in the examples below. These examples are not intended to limit the scope of the present invention and are presented for illustrative purposes.
Example; 1 st Layer:
nd Layer (inert
3rd Layer:
Thiocolchicoside 8.0 mg
Lactose monohydrate 1 14.0 mg
Corn starch 20.0 mg
Gelatin 200 Bloom 2.0 mg
Sugar 2.0 mg
Talk 2.5 mg
Magnesium stearate 1 .5 mg
The total weight of the third
150.0 mg layer: Production method:
1 st Layer: Spray granulation:
Weighed amounts of nimesulide, lactose monohydrate, microcrystalline cellulose PH 101 , and sodium starch glycolate are taken to a fluidized bed dryer. An aqueous solution of hydroxypropyl cellulose (Klucell LF) is prepared, this solution is sprayed to the fluidized bed dryer (spray granulation), dried, the dried granules are ground, transferred to an intermediate bulk container (IBC), magnesium stearate is introduced to the mixture and stirred for 5 more minutes.
2nd Layer (inert layer): direct mix
Weighed amounts of a part of microcrystalline cellulose (PH 102) and hydroxypropyl cellulose (LH1 1 ) are taken to the intermediate bulk container. Iron oxide yellow, colloidal silicon dioxide and microcrystalline cellulose (PH 102) (the remaining part) is passed through a 630 μηι sieve and introduced to the IBC. The powder mixture is stirred in the mixer for 20 minutes. Magnesium stearate is added to this mixture and stirred for 5 more minutes. 3rd Layer: Wet granulation
Weighed amounts of thiocolchicoside, lactose monohydrate, corn starch, and sieved sugar are taken to a Collette and mixed. An aqueous solution of a weighed amount of gelatin is prepared and added to the dry mixture and wet granulation is performed. The wet granules are passed through a 8 mm sieve and ground. The ground material is dried in a drying oven to a moisture content of 3.0% at most. The dried granules are passed through a 2.0 mm dry grinder, the content is taken to a dry mixer and a dry grinding process is carried out. Talk is added to the container to which the granules are transferred and stirred for 15 minutes. Magnesium stearate is added to the mixture and stirred for 5 more minutes.
Thus, the multilayer tablets are made using the amounts given above for each layer.

Claims

A multilayer oral tablet formulation comprising nimesulide or a pharmaceutically acceptable salt thereof and thiocolchicoside or a pharmaceutically acceptable salt thereof.
The tablet formulation according to claim 1 , wherein said formulation has an immediate release layer comprising nimesulide, has an immediate release layer or controlled release layer comprising thiocolchicoside, and has an inert layer separating these two layers from each other.
The tablet formulation according to claim 2, wherein said formulation has an immediate release layer comprising nimesulide, has an immediate release layer comprising thiocolchicoside, and has an inert layer separating these two layers from each other.
The tablet formulation according to claims 2-3, wherein the inert layer comprises cellulosic polymers.
The tablet formulation according to claim 4, wherein the cellulosic polymers are hydroxypropyl cellulose and microcrystalline cellulose.
The tablet formulation according to claim 1 -5, wherein the amount of the disintegrant is 1 .0 to 30.0% in the nimesulide comprising-layer, 3.0 to 35.0% in the thiocolchicoside comprising-layer.
The tablet formulation according to claim 6, wherein the amount of the disintegrant is 2.0 to 20.0% in the nimesulide comprising-layer, 5.0 to 25.0% in the thiocolchicoside comprising-layer.
The tablet formulation according to claim 7, wherein the disintegrant is selected from a group comprising alginic acid and alginates, ion-exchange resins, magnesium aluminum silicate, sodium dodecyl sulfate, sodium carboxymethyl cellulose, croscarmellose sodium, cross linked polyvinylpyrrolidone, carboxymethylcellulose calcium, docusate sodium, guar gum, corn starch, polacrilin potassium, poloxamer, povidone, sodium alginate, sodium glycine carbonate, sodium lauryl sulfate, sodium starch glycolate, or the mixtures thereof.
9. The tablet formulation according to claims 1 -8, further comprising at least one pharmaceutically-acceptable excipient selected from a group consisting of fillers, binders, lubricants, glidants, flavoring agents, sweeteners, and coloring agents.
10. The tablet formulation according to claim 9, wherein the filler is selected from a group comprising mannitol, spray-dried mannitol; polysaccharides such as microcrystalline cellulose; dibasic calcium phosphate dihydrate, lactose, sugars, sorbitol, lactose monohydrate; a mixture of microcrystalline cellulose and guar gum; a mixture of mannitol, polyplasdone and syolid; a mixture of mannitol, crospovidone and polyvinyl acetate; inorganic salts such as isomalt, sucrose, calcium salts, or the mixtures thereof.
1 1 . The tablet formulation according to claim 10, wherein the amount of the filler is 2.0 to 90.0%, preferably 10.0 to 85.0%, and more preferably 15.0 to 80.0% of the total weight of the tablet.
12. The tablet formulation according to claim 9, wherein the binder is selected from a group comprising natural gums, starch, gelatin, polyvinylpyrrolidone, polymethacrylates; collagen, proteins such as gelatin; semisynthetic polymers such as agar, alginate, sodium alginate, pectin, starch, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose; synthetic polymers such as carbomer, poloxamer, polyacrylamide, polyvinyl alcohol; inorganic substances such as aluminum hydroxide, bentonite, laponite; starch mucilage, acacia mucilage, polydextrose, polyethylene oxide, or the mixtures thereof.
13. The tablet formulation according to claim 12, wherein the amount of the binder is 0.001 to 55.0%, preferably 0.1 to 30.0% of the total weight of the tablet.
14. The tablet formulation according to Claim 9, wherein the lubricant and glidant are selected from a group comprising sodium stearyl fumarate, magnesium stearate, polyethylene glycol, colloidal silicon dioxide, stearic acid, talk, metal stearates, boric acid, sodium chloride benzoate and acetate, sodium or magnesium lauryl sulfate, or the mixtures thereof.
15. The tablet formulation according to claim 14, wherein the total amount of the lubricant and the glidant is 0.01 to 20.0%, preferably 0.1 to 10.0% of the total weight of the tablet.
16. A pharmaceutical formulation according to any of the preceding claims for use in the treatment and prevention of osteoarthritis, pain associated with tissue trauma following osteoarthritis surgery, psoriatic arthritis, rheumatoid arthritis, myalgia, bone pain, arthralgia, muscle spasms, soft tissue traumas, lumbago, back pain, sciatica and torticollis.
EP14705127.0A 2013-02-15 2014-02-14 Oral pharmaceutical formulations comprising nimesulide and thiocolchicoside Withdrawn EP2956125A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201301875 2013-02-15
PCT/EP2014/052948 WO2014125085A1 (en) 2013-02-15 2014-02-14 Oral pharmaceutical formulations comprising nimesulide and thiocolchicoside

Publications (1)

Publication Number Publication Date
EP2956125A1 true EP2956125A1 (en) 2015-12-23

Family

ID=49305059

Family Applications (1)

Application Number Title Priority Date Filing Date
EP14705127.0A Withdrawn EP2956125A1 (en) 2013-02-15 2014-02-14 Oral pharmaceutical formulations comprising nimesulide and thiocolchicoside

Country Status (2)

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EP (1) EP2956125A1 (en)
WO (1) WO2014125085A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112393827A (en) * 2019-08-12 2021-02-23 南京理工大学 Preparation method of biodegradable piezoelectric force sensor

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3173077B1 (en) 2015-11-30 2020-05-06 Sanovel Ilac Sanayi ve Ticaret A.S. Tablet formulations of nimesulide and thiocolchicoside
TR201906487A1 (en) * 2019-04-30 2020-11-23 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi PHARMACEUTICAL COMPOSITIONS CONTAINING TOLPERISONE AND NIMESULIDE COMBINATIONS

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Publication number Priority date Publication date Assignee Title
FR2725134B1 (en) 1994-10-04 1996-12-20 Lederle Lab NEW PHARMACEUTICAL ASSOCIATION BASED ON IBUPROFEN AND THIOCOLCHICOSIDE
FR2735369B1 (en) 1995-06-13 1997-07-11 Synthelabo PHARMACEUTICAL COMPOSITIONS BASED ON SODIUM SALT OF DICLOFENAC AND THIOCOLCHICOSIDE
IT1291278B1 (en) 1996-07-05 1999-01-07 Errekappa Euroterapici S P A NIMESULIDE-BASED PHARMACEUTICAL PREPARATION FOR TOPICAL USE
TR200708925A1 (en) * 2007-12-26 2009-07-21 Sanovel İlaç Sanayi̇ Ve Ti̇caret Anoni̇m Şi̇rketi̇ Combinations of flurbiprofen and muscle relaxants for controlled release
TR200903036A2 (en) * 2009-04-17 2010-06-21 Mustafa Nevzat İlaç San.A.Ş. Combinations of thiocolchicoside and non-steroidal anti-inflammatory drugs
TR201001903A2 (en) * 2010-03-12 2011-04-21 Ali̇ Rai̇f İlaç Sanayi̇ Ve Ti̇caret A.Ş. Extended release thiocolchicoside tablet.

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None *
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112393827A (en) * 2019-08-12 2021-02-23 南京理工大学 Preparation method of biodegradable piezoelectric force sensor

Also Published As

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