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EP3197434A1 - Combinaisons associant du loxoprofène et des médicaments antispasmodiques - Google Patents

Combinaisons associant du loxoprofène et des médicaments antispasmodiques

Info

Publication number
EP3197434A1
EP3197434A1 EP15780776.9A EP15780776A EP3197434A1 EP 3197434 A1 EP3197434 A1 EP 3197434A1 EP 15780776 A EP15780776 A EP 15780776A EP 3197434 A1 EP3197434 A1 EP 3197434A1
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical composition
pharmaceutically acceptable
composition according
loxoprofen
acceptable salt
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Withdrawn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
EP15780776.9A
Other languages
German (de)
English (en)
Inventor
Ali TÜRKYILMAZ
Yelda Erdem
Seval Ataman
Ayse ILDES ERDEM
Gaye Ramazanoglu
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 EP3197434A1 publication Critical patent/EP3197434A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • A61K31/433—Thidiazoles
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
    • 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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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

  • This invention is a novel pharmaceutical composition
  • loxoprofen or a pharmaceutically acceptable salt thereof in combination with antispastic drugs or pharmaceutically acceptable salts thereof with anti-inflammatory, analgesic and myorelaxant activity.
  • Loxoprofen is a non-steroidal anti-inflammatory drug in the propionic acid derivatives group. It is a prodrug and it is quickly converted to its active trans-alcohol metabolite following oral administration. It is a non-selective cyclooxygenase inhibitor and works by reducing the synthesis of prostaglandins from arachidonic acid. Its chemical name is (RS)-2- ⁇ 4-[(2-oxocyclopentyl)methyl]phenyl ⁇ propanoic acid and its chemical structure is shown in the Formula I.
  • the patent EP0947584 (B1 ) discloses an anti-inflammatory analgesic patch comprising loxoprofen or pharmaceutically acceptable salt thereof, water, crotamiton and a water soluble polymer.
  • the patent application WO0247661 discloses pharmaceutical composition for intramuscular injection containing loxoprofen or a pharmaceutically acceptable salt thereof, as an active ingredient.
  • the patent EP1806152 discloses an external preparation containing a pharmacologically active component that is loxoprofen and a lipophilic polyglycerin fatty acid ester.
  • Spasticity is defined as an upper motor neuron disorder, possibly caused by a conduction interruption in the nerve pathway.
  • Antispastic drugs are primarily used to treat neurological disorders, such as cerebral palsy.
  • Tizanidine, dantrolene, baclofen, diazepam, methocarbamol, succinylcholine, quinine are known as antispastic drugs used in the treatment of painful muscle spasms and spasticity occurring in musculoskeletal and neuromuscular disorders and for treating contractures and inflammatory conditions that affect the muscular system.
  • Tizanidine is an example for antispastic drugs. Its chemical structure is shown in Formula II.
  • Tizanidine is a a 2 -adrenergic agonist and acts mainly at spinal and supraspinal levels to inhibit excitatory interneurones. It is used for the symptomatic relief of spasticity associated with multiple sclerosis or with spinal cord injury or disease.
  • the recommended dose of tizanidin is 2 mg, 4mg or 6 mg.
  • United Kingdom patent application GB 2 197 198 A1 (Sandoz Ltd.) 03.1 1 .1986, describes novel pharmaceutical preparations comprising ibuprofen and tizanidine with analgesic and myotonolytic activity as well as to methods of inducing analgesia and of treating conditions associated with increased muscle tone.
  • the composition is preferably formulated as a tablet and desirably the weight ratio of tizanidine to ibuprofen is from 1 :50 to 1 :200, especially 1 :100.
  • Dantrolene is also an antispastic drug indicated in controlling the manifestations of clinical spasticity resulting from upper motor neuron disorders (e.g., spinal cord injury, stroke, cerebral palsy, or multiple sclerosis). Its chemical structure is shown in Formula III.
  • the recommended dose of dantrolene is 25 mg to 100 mg four times a day and at bedtime. It is well known that drugs used in the same therapeutic area or even for treating the same indication cannot always be combined a priori with the expectation of at least additive therapeutic effects.
  • the scientific literature is full of examples wherein compounds of different classes, which are used to treat the same indications, cannot be combined into safe and efficacious dosage forms thereby resulting in incompatible drug combinations. The reasons for this unexpected lack of compatibility are varied; however, it is often found that the incompatible drug combinations result in increased side effects, unwanted drug interactions or new side effects. More specifically, in the area of analgesia there are drug combinations that are contraindicated for some or all of these very same reasons.
  • Antispastic drugs have been evaluated alone or in combination with conventional analgesics for the treatment of pain. Mixed and unpredictable results have been obtained in a pharmaceutical composition. But loxoprofen has not previously been combined with antispastic drugs, in particular with tizanidine or dantrolone in a pharmaceutical composition for the treatment of inflammatory, pain and musculoskeletal diseases.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising loxoprofen or a pharmaceutically acceptable salt thereof in combination with antispastic drugs or pharmaceutically acceptable salts thereof with anti-inflammatory, analgesic and myorelaxant activity.
  • pharmaceutical composition is administrated orally, parenterally, intramuscularly and topicaly in tablet, bilayer tablet, multi layer tablet, capsule, sachet, injectable preparat, suspension, syrup, ointment, cream or gel form.
  • the present composition is in the form of a tablet, bilayer tablet or a capsule.
  • Novel pharmaceutical composition in the form of a tablet or a capsule administrated orally may provide a significant advance in the available treatments.
  • Such combination therapy may also provide therapeutic improvements owing to the potential synergistic effect provided by the combination.
  • this invention comprises active ingredient, loxoprofen or a pharmaceutically acceptable salt thereof in combination with antispastic drugs or pharmaceutically acceptable salts thereof.
  • antispastic drugs are selected from the group comprising, tizanidine, dantrolene, baclofen, diazapem, methocarbamol, succinylcholine, quinine.
  • they are tizanidine or dantrolene or pharmaceutically acceptable salts thereof.
  • this invention comprises loxoprofen or a pharmaceutically acceptable salt thereof in combination with tizanidine or a pharmaceutically acceptable salt thereof wherein the loxoprofen is present in an amount of between 10.0% and 45.0% and the tizanidine is present in an amount of 0.5% and 10.0% (w/w), preferred amount of the loxoprofen is between 20.0% and 35.0% and the tizanidine is between 1 .0 % and 5.0% (w/w).
  • this invention comprises loxoprofen or a pharmaceutically acceptable salt thereof in combination with dantrolene or a pharmaceutically acceptable salt thereof wherein the loxoprofen is present in an amount of between 10.0% and 45.0% and the dantrolene is present in an amount of 1 .0% and 50.0% (w/w), preferred amount of the loxoprofen is between 20.0% and 35.0% and the dantrolene is between 5.0 % and 30.0 % (w/w).
  • the pharmaceutical composition is a bilayer tablet having the loxoprofen in one layer and antispastic drugs especially tizanidine or dantrolene in another layer.
  • the amount of loxoprofen or a pharmaceutically acceptable salt thereof employed in such bilayer tablets preferably ranges from 10.0% to 45.0%, and more preferably is 20.0% to 35.0% (w/w).
  • the amount of tizanidine or a pharmaceutically acceptable salt thereof employed in such bilayer tablets preferably ranges from 0.5 % to 10.0% and more preferably is 1 .0% to 5.0% (w/w).
  • the amount of dantrolene or a pharmaceutically acceptable salt thereof employed in such bilayer tablets preferably ranges from 1 .0% to 50.0% and more preferably is 5.0% to 30.0% (w/w).
  • the pharmaceutically acceptable salt of loxoprofen is sodium hydrate and the pharmaceutically acceptable salt of tizanidine is hydrochloride salt and the pharmaceutically acceptable salt of dantrolene is sodium salt.
  • the main challenges when combining two or more molecules in the same pharmaceutical form are (a) to guarantee the physicochemical compatibility between the different active ingredients and/or between the active ingredients and the excipients used; and (b) to insure the therapeutical compatibility between the two active ingredients regarding their pharmacokinetic and/or pharmaceutical properties in order that the posology of the combined composition allows to obtain safe and efficient plasma levels of both pharmacological agents.
  • the pharmaceutical composition comprising loxoprofen in combination with antispastic drugs, especialy with tizanidin or dantrolene have an additive analgesic effect in relief of postoperative pain and provide greater analgesia with the results in a lower incidence of side effects according to priori.
  • These pharmaceutical combinations are administrated orally, parenterally, intramuscularly and topically.
  • compositions of the invention include tablets, capsules, injectables, suspensions, syrups, sachets, ointments, creams or gels can be made in accordance with methods that are standard in the art.
  • oral dosage forms include tablets (comprising bilayer or multilayer and coated or uncoated), capsules, hard or soft gelatin capsules, pellets, pills, powders, granules, elixirs, tinctures, colloidal dispersions, dispersions, effervescent compositions, films, sterile solutions, suspensions, syrups or emulsions.
  • the combination of a loxoprofen with tizanidine or dantrolene will be in the form of a conventional tablet or capsule. And it may be granulated by methods such as, dry granulation, low- or high- shear granulation, wet granulation or fluidized-bed granulation. Low-shear granulation, high-shear granulation, wet granulation and fluidized- bed granulation generally produce harder, less friable tablets.
  • this invention comprises, the combination of loxoprofen or a pharmaceutically acceptable salt and antispastic drugs or pharmaceutically acceptable salts with at least one pharmaceuticlly acceptable excipient.
  • Suitable pharmaceutically acceptable excipients comprise but are not limited to disintegrants, fillers, binders, glidants and lubricants or mixtures thereof.
  • said disintegrants comprise, but are not limited to microcrystalline cellulose, low-substituted hydroxypropyl cellulose, alginic acid and alginates, ion-exchange resins, magnesium aluminum silica, sodium carboxy methyl cellulose, carboxy methyl cellulose calcium, polyvinylpyrrolidone, docusate sodium, guar gum, polacrilin potasium, poloxomer, sodium alginate, sodium glysin carbonate, or the mixtures thereof.
  • it is microcrystalline cellulose.
  • said fillers comprise, but are not limited to lactose monohydrate, dibasic calcium phosphate, tribasic calcium phosphate, sorbitol, sucrose, trehalose, isomalt, microcrystalline cellulose, mannitol, starch, sodium carbonate, sodium bicarbonate, dextrose, maltodextrine, calcium carbonate, xylitol or the mixtures thereof.
  • lactose monohydrate dibasic calcium phosphate, tribasic calcium phosphate, sorbitol, sucrose, trehalose, isomalt, microcrystalline cellulose, mannitol, starch, sodium carbonate, sodium bicarbonate, dextrose, maltodextrine, calcium carbonate, xylitol or the mixtures thereof.
  • it is lactose monohydrate.
  • said binders comprise, but are not limited to hydroxypropyl cellulose, pregelatinised starch, sugars, glycose syrups, natural gums, guar gum, gelatins, pullulan, polymetacrylates, collagen, agar, algynate, sodium alginate, hyaluronic acid, pectin, tragacanth gum, carboxymethyl cellulose, polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, polyvinyl acetate and their copolymers, hydroxypropyl methyl cellulose, carboxy methyl cellulose, methyl cellulose, microcrystalline cellulose, polyvinylalcohol, carrageenan, carbomer, poloxamer, polyacrylamide, aluminum hydroxide, benthonite, laponite, setostearyl alcohol, polyoxyethylene-alkyl ethers, acacia mucilage, polydextrose, polyethylene oxide or the mixtures thereof.
  • said glidants comprise, but are not limited to colloidal silicon dioxide, stearic acid, talk, aluminium silicate or the mixtures thereof.
  • it is colloidal silicon dioxide.
  • said lubricants comprise, but are not limited to stearic acid, magnesium stearate, sodium stearyl fumarate, sodium lauryl sulphate, magnesium lauryl sulphate, fumaric acid, glyceryl palmitostearate, hydrogenated natural oils, zinc stearate, calcium stearate, silica, talc, polyethylene glycol, paraffin or the mixtures thereof.
  • it is stearic acid.
  • compositions comprising loxoprofen in combination with antispastic drugs, especially tizanidine or dantrolene for use in the treatment of painful muscle spasms associated with static and functional disorders of vertebra or occurred in post-operations of osteoarthritis, pain and inflammatory symptoms associated with tissue trauma, degenerative vertebra diseases as torticollis, dorsalgia, lombalgia, disk hernia, neurologic and traumatic disorders associated with spasticity.
  • antispastic drugs especially tizanidine or dantrolene for use in the treatment of painful muscle spasms associated with static and functional disorders of vertebra or occurred in post-operations of osteoarthritis, pain and inflammatory symptoms associated with tissue trauma, degenerative vertebra diseases as torticollis, dorsalgia, lombalgia, disk hernia, neurologic and traumatic disorders associated with spasticity.
  • loxoprofen sodium hydrate, lactose monohydrate, hydroxypropyl cellulose (LF) and microcrystalline cellulose are sieved and mixed. After obtaining the homogenous mixture, wet granulation process is applied with water and then dried in an oven at 55°C. The obtained granul is then sieved and tizanidine hydrochloride, stearic acid and colloidal silicon dioxide are sieved and added to granules then mixed again. Total mixture is pressed into tablets. These tablets are optionally coated with conventional coating polymers of Opadry II.
  • these powder mixtures are filled in a capsule by capsule filling machine to obtain conventional capsule forms in appropriate lenght.
  • loxoprofen sodium hydrate, lactose monohydrate, hydroxypropyl cellulose (LF) and microcrystalline cellulose are sieved and mixed. After obtaining the homogenous mixture, wet granulation process is applied with water and then dried in an oven at 55°C. The obtained granul is then sieved and dantrolene sodium, stearic acid and colloidal silicon dioxide are sieved and added to granules then mixed again. Total mixture is pressed into tablets. These tablets are optionally coated with conventional coating polymers of Opadry II.
  • the process of the composition is carried out as follows: Loxoprofen sodium hydrate and polyvinylpyrrolidone is mixed with water to prepare the solution 1 and solution 1 is sprayed on to sugar pellets to obtain loxoprofen pellets. Tizanidine hydrochloride, hydroxypropyl methyl cellulose and triethly citrate is mixed with water to prepare the solution 2 and solution 2 is sprayed on to sugar pellets to obtain tizanidine pellets. Obtained pellets are filled into capsules.
  • Quantum Sufficiat (sufficient quantity)
  • the process of the composition is carried out as follows: Loxoprofen sodium hydrate, polyvinylpyrrolidone, tizanidine hydrochloride and triethly citrate is mixed with water to prepare a solution and the solution is then sprayed on to sugar pellets to obtain loxoprofen and tizanidine pellets. Obtained pellets are filled into capsules.
  • Quantum Sufficiat (sufficient quantity)
  • Loxoprofen sodium hydrate and polyvinylpyrrolidone is mixed with water to prepare the solution 1 and solution 1 is sprayed on to sugar pellets to obtain loxoprofen pellets.
  • Dantrolene sodium, hydroxypropyl methyl cellulose and triethly citrate is mixed with water to prepare the solution 2 and solution 2 is sprayed on to sugar pellets to obtain dantrolene pellets. Obtained pellets are filled into capsules.
  • composition is carried out as follows: Loxoprofen sodium hydrate, polyvinylpyrrolidone, dantrolene sodium and triethly citrate is mixed with water to prepare a solution and the solution is then sprayed on to sugar pellets to obtain loxoprofen and dantrolene pellets. Obtained pellets are filled into capsules.

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une nouvelle composition pharmaceutique comprenant du loxoprofène, ou un sel de qualité pharmaceutique de celui-ci, en association avec des médicaments antispasmodiques, ou des sels de qualité pharmaceutique de ceux-ci, présentant une activité anti-inflammatoire, analgésique et myorelaxante.
EP15780776.9A 2014-09-24 2015-09-22 Combinaisons associant du loxoprofène et des médicaments antispasmodiques Withdrawn EP3197434A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201411290 2014-09-24
PCT/EP2015/071694 WO2016046189A1 (fr) 2014-09-24 2015-09-22 Combinaisons associant du loxoprofène et des médicaments antispasmodiques

Publications (1)

Publication Number Publication Date
EP3197434A1 true EP3197434A1 (fr) 2017-08-02

Family

ID=52706265

Family Applications (1)

Application Number Title Priority Date Filing Date
EP15780776.9A Withdrawn EP3197434A1 (fr) 2014-09-24 2015-09-22 Combinaisons associant du loxoprofène et des médicaments antispasmodiques

Country Status (2)

Country Link
EP (1) EP3197434A1 (fr)
WO (1) WO2016046189A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10813916B2 (en) * 2015-05-29 2020-10-27 Jubilant Generics Limited Immediate release pharmaceutical composition of tizanidine
JP6991880B2 (ja) * 2018-02-14 2022-01-13 エスエス製薬株式会社 医薬組成物
CN113081997A (zh) * 2021-04-01 2021-07-09 杭州泓友医药科技有限公司 一种盐酸替扎尼定胶囊剂及其制备方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4161538A (en) 1977-04-05 1979-07-17 Sankyo Company Limited Substituted phenylacetic acid derivatives and process for the preparation thereof
NL8702523A (nl) 1986-11-03 1988-06-01 Sandoz Ag Farmaceutische preparaten met analgetische werking en werkwijze voor het bereiden of vervaardigen en toepassen van deze preparaten.
US5260337A (en) * 1992-07-29 1993-11-09 Merck & Co., Inc. Ibuprofen-muscle relaxant combinations
JPH10120560A (ja) 1996-08-26 1998-05-12 Sankyo Co Ltd ロキソプロフェン含有外用製剤
KR100405161B1 (ko) 2000-12-14 2003-11-12 신풍제약주식회사 록소프로펜 함유 근육주사제 조성물
JP5025268B2 (ja) 2004-11-10 2012-09-12 久光製薬株式会社 外用製剤及び貼付剤
TR200703092A1 (tr) * 2007-05-08 2008-12-22 SANOVEL �LA� SAN. VE TiC. A.�. Flurbiprofen ve kas gevşetici kombinasyonları
WO2012173581A1 (fr) * 2011-03-21 2012-12-20 Ak Kimya Ithalat-Ihracat Ve Sanayii A.S. Combinaisons de thiocolchicoside, étodolac et famotidine
JP2014094894A (ja) * 2012-11-07 2014-05-22 Kowa Company Ltd 安定な医薬組成物

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