WO2015093515A1 - １－インダンスルファミド誘導体を含む疼痛の治療および／または予防剤 - Google Patents

１－インダンスルファミド誘導体を含む疼痛の治療および／または予防剤 Download PDF

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Publication number
WO2015093515A1
WO2015093515A1 PCT/JP2014/083374 JP2014083374W WO2015093515A1 WO 2015093515 A1 WO2015093515 A1 WO 2015093515A1 JP 2014083374 W JP2014083374 W JP 2014083374W WO 2015093515 A1 WO2015093515 A1 WO 2015093515A1
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pain
administration
mmol
dihydro
added
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English (en)
French (fr)
Japanese (ja)
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浩之 東山
数田　雄二
敬輔 橋本
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Eisai R&D Management Co Ltd
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Eisai R&D Management Co Ltd
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Priority to SG11201604484UA priority Critical patent/SG11201604484UA/en
Priority to RU2016122189A priority patent/RU2678571C1/ru
Priority to ES14871860.4T priority patent/ES2673876T3/es
Priority to CA2932529A priority patent/CA2932529C/en
Priority to KR1020167014850A priority patent/KR102250214B1/ko
Priority to BR112016012833-8A priority patent/BR112016012833B1/pt
Priority to AU2014367781A priority patent/AU2014367781B2/en
Priority to EP14871860.4A priority patent/EP3085369B1/en
Priority to US15/102,046 priority patent/US9610262B2/en
Priority to MX2016007370A priority patent/MX370898B/es
Application filed by Eisai R&D Management Co Ltd filed Critical Eisai R&D Management Co Ltd
Priority to JP2015553575A priority patent/JP6518595B2/ja
Priority to CN201480066081.3A priority patent/CN105792821B/zh
Publication of WO2015093515A1 publication Critical patent/WO2015093515A1/ja
Priority to IL246036A priority patent/IL246036B/en
Anticipated expiration legal-status Critical
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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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to a therapeutic and / or prophylactic agent for pain comprising a 1-indanesulfamide derivative, a salt thereof, or a prodrug thereof.
  • Pain Pain is defined by the International Pain Society as “the unpleasant sensation that is expressed when or when there is actually any tissue damage, or when such damage occurs, It is defined as “unpleasant emotional experience” (Non-Patent Document 1).
  • Pain Pain (pain) is generally classified into acute pain and chronic pain. Acute pain is pain that persists within 3 months. Acute pain often begins sharply and exhibits sharp pain. Acute pain is caused by many events and circumstances, such as surgery, fractures, dental treatments, burns and cuts. Chronic pain is pain that persists for more than 3 months. Common chronic pain includes headache, low back pain, cancer pain, joint pain, neuropathic pain, psychogenic pain (past illness, trauma and other pains that cause no physical pain) Seen in Here, neuropathic pain is a Japanese translation of Neuropathic pain, which has been translated as neuropathic pain, and is refractory caused by damage or disease of the peripheral or central somatosensory nervous system. For example, diabetic neuropathy, trigeminal neuropathy, postherpetic neuralgia, etc. (Non-Patent Documents 2 and 3).
  • Analgesics are roughly divided into the following three categories: (1) opioid analgesics, (2) non-opioid analgesics such as steroidal anti-inflammatory drugs, acetaminophen, dipyrone, etc. (3) analgesics (The main pharmacological action has no analgesic action, and when used in combination with an analgesic, it increases the analgesic effect and is known to exhibit an analgesic effect under certain circumstances).
  • opioid analgesics act on opioid receptors in the central nervous system to produce strong analgesic effects, their use is limited due to serious side effects and dependence.
  • Non-opioid analgesics have analgesic effects, but their effects are weak and various side effects may occur. Furthermore, no effective therapeutic agent has yet been found for chronic pain such as diabetic neuropathy, trigeminal neuropathy, shingles, etc., and these acute pain and chronic pain were included. Therefore, the development of an effective drug for a wide range of pains is awaited.
  • Non-patent Documents 4 and 5 Treatment of insufficient acute pain causes various symptoms such as anxiety, depression, insomnia, fatigue, decreased appetite, vomiting and vomiting.
  • acute pain that is not alleviated progresses to chronic pain.
  • Non-Patent Document 6 Chronic pain is currently an important public health problem because about 40% of chronic pain cannot be fully relieved. Therefore, effective treatment of acute and chronic pain remains an unmet medical need for many patients. Therefore, development of a therapeutic agent effective for acute pain and chronic pain is eagerly desired.
  • Non-patent Document 7 rat strangulation nerve injury model (CCI model) and the like are known as chronic pain models. If classified according to the cause of pain, the CCI model is considered to be a pathological model corresponding to neuropathic pain (Non-Patent Document 8).
  • Patent Documents 1 and 2 low-molecular compounds described in Patent Documents 1 and 2 are known as sulfamide derivatives having analgesic activity.
  • a 1-indancerfamide derivative having analgesic action is not known.
  • An object of the present invention is to provide an agent for treating and / or preventing pain that exhibits analgesic action in various animal models and has applicability to a wide range of pains.
  • the present inventors conducted a study using a mouse hot plate test for confirming the analgesic effect on acute pain and a rat CCI model for confirming the analgesic effect on chronic pain.
  • the 1-indantholfamide derivative has an effect of suppressing acute pain induced by noxious stimuli.
  • 1-indanthrufamide derivatives have an effect of suppressing chronic pain induced by nerve ligation, and the present invention was completed.
  • the present invention 1) a therapeutic and / or prophylactic agent for pain comprising one compound selected from the following group or a pharmaceutically acceptable salt thereof: (1) N-[(1S) -2,2,5,7-tetrafluoro-2,3-dihydro-1H-inden-1-yl] sulfamide, (2) (-)-N- (7-chloro-2,2,5-trifluoro-2,3-dihydro-1H-inden-1-yl) sulfamide, (3) N-[(1S) -2,2-difluoro-7-methyl-2,3-dihydro-1H-inden-1-yl] sulfamide, and (4) N-[(1S) -2,2 , 5-trifluoro-7-methyl-2,3-dihydro-1H-inden-1-yl] sulfamide; 2) The therapeutic and / or prophylactic agent according to 1) above, wherein the pain is acute pain or chronic pain; 3) The therapeutic and / or prophy
  • the drug of the present invention exhibits an action of suppressing acute pain induced by noxious stimulation in a mouse hot plate test. Moreover, in a rat CCI model, the effect
  • the 1-indanesulfamide compound used in the present invention may have a crystal polymorph, but is not limited to a specific crystal form, and is a single substance of any crystal form. It may be a mixture or a mixture, and an amorphous material is also included. Furthermore, the compounds according to the present invention may form pharmaceutically acceptable salts and various solvates.
  • the “pharmaceutically acceptable salt” is not particularly limited as long as it forms a salt with the compound used in the present invention and is pharmaceutically acceptable.
  • Solidvate means that the solvent used in the reaction or crystallization is in a state of being incorporated into the crystal without forming a covalent bond with the molecule or ion of the compound.
  • solvates include hydrates and alcohol (ethanol) solvates.
  • the raw material compounds, intermediates and various reagents in the production of the compounds used in the present invention may form salts and solvates, all of which vary depending on the starting materials, the solvent used, etc., and do not inhibit the reaction.
  • the solvent to be used is not particularly limited as long as it varies depending on starting materials, reagents and the like, and can dissolve the starting material to some extent without inhibiting the reaction.
  • the compound used in the present invention is obtained as a free form, it can be converted into a salt or a solvate thereof which may be formed by the compound used in the present invention according to a conventional method.
  • various isomers for example, geometric isomers, optical isomers, rotational isomers, stereoisomers, tautomers, etc.
  • obtained for the compounds or intermediates used in the present invention can be obtained by conventional separation means, For example, it can be purified and isolated by using recrystallization, diastereomeric salt method, enzyme resolution method, various chromatography (eg, thin layer chromatography, column chromatography, gas chromatography, etc.).
  • the compound used in the present invention or a pharmaceutically acceptable salt thereof can be formulated by a conventional method.
  • the dosage form include oral preparations (tablets, granules, powders, capsules, syrups). Agents), sublingual tablets, injections (for intravenous administration, intramuscular administration, subcutaneous administration, intraperitoneal administration, intraarticular administration, epidural administration), external preparations (percutaneous absorption preparation ( Ointments, patches, nasal drops, suppositories, etc.).
  • solid preparations such as tablets, capsules, granules, and powders are usually 0.001 to 99.5% by weight, preferably 0.01 to 90% by weight of the compound used in the present invention or its pharmacology. Which can be included in a chemically acceptable form.
  • the compound used in the present invention or a pharmaceutically acceptable salt thereof if necessary, an excipient, a binder, a disintegrant, a lubricant, a coloring agent.
  • An agent etc. can be added and it can be set as a tablet, a granule, a powder, a capsule by a conventional method. These preparations may be coated with a film as necessary.
  • excipients include lactose, corn starch, and crystalline cellulose.
  • binders include hydroxypropyl cellulose and hydroxypropylmethyl cellulose.
  • disintegrants include carboxymethyl cellulose calcium and croscarmellose sodium. Can be mentioned.
  • Examples of the lubricant include magnesium stearate and calcium stearate, and examples of the colorant include titanium oxide.
  • Examples of the film coating agent include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose and the like.
  • any of the above-mentioned additives is not limited to these.
  • the compound used in the present invention or its drug Add pH adjusters, buffers, suspending agents, emulsifiers, solubilizers, antioxidants, preservatives (preservatives), isotonic agents, etc., as necessary to the salts that are pharmaceutically acceptable.
  • it can be produced by a conventional method.
  • it may be freeze-dried to obtain a freeze-dried preparation that is dissolved at the time of use.
  • These injections can be administered intravenously, subcutaneously, intramuscularly and the like.
  • pH adjusters and buffers include organic acids or inorganic acids and / or salts thereof
  • suspending agents include methyl cellulose, polysorbate 80, sodium carboxymethyl cellulose, and the like.
  • emulsifiers include: Polyoxyethylene castor oil derivative, hydroxypropyl cellulose, lecithin and the like, for example, polysorbate 80, polyoxyethylene sorbitan monolaurate and the like as solubilizing agents, and as the antioxidant, for example ⁇ -tocopherol and the like
  • examples of the preservative include methyl paraoxybenzoate and ethyl paraoxybenzoate
  • examples of the isotonic agent include glucose, sodium chloride, mannitol and the like, but are not limited thereto.
  • injections can usually contain 0.00001 to 99.5% by weight, preferably 0.0001 to 90% by weight of the compound used in the present invention or a pharmaceutically acceptable salt thereof.
  • a base material is added to the compound used in the present invention or a pharmaceutically acceptable salt thereof, and if necessary, the above-mentioned emulsifier, preservative, pH adjuster.
  • a percutaneous absorption preparation an ointment, a patch, etc.
  • a nasal drop, a suppository, etc. can be produced by adding a colorant and the like by a conventional method.
  • various raw materials usually used for pharmaceuticals, quasi drugs, cosmetics and the like can be used.
  • animal and vegetable oils, mineral oils, ester oils, waxes, higher alcohols, purified water And other raw materials can be used.
  • These external preparations can usually contain 0.00001 to 99.5% by weight, preferably 0.0001 to 90% by weight of the compound used in the present invention or a pharmaceutically acceptable salt thereof.
  • the dose of the pharmaceutical agent according to the present invention usually varies depending on symptoms, age, sex, weight, etc., but may be an amount sufficient for producing a desired effect.
  • about 0.1 to 5000 mg (preferably 0.5 to 1000 mg, more preferably 1 to 600 mg) per day is once per day or 2 to 6 times a day. Used in divided times.
  • the compound used in the present invention can be produced, for example, by the method described in the following production examples, and the effect of the compound can be confirmed by the method described in the following test examples.
  • a compound with a document name or the like is shown to have been produced according to the document or the like.
  • Root temperature in the following production examples usually indicates about 10 ° C. to about 35 ° C. % Indicates weight percent unless otherwise specified. However, the ratio of the solvent in silica gel chromatography indicates the volume ratio of the solvent to be mixed.
  • an HPLC system manufactured by GILSON pump; master pump Model 305, slave pump Model 306, pump head 50SC, dynamic mixer Model 811D / A, pressure module Model 806, UV detector; UV-VIS detector Model 155, injector, fraction collector; Model 215, column: CHIRALPAK (registered trademark) AD-H, IA, IB, IC, ID, IE, IF manufactured by DAICEL, CHIRALCEL (registered trademark) OD-H, OJ- manufactured by DAICEL Any of H, column size: 2 cm ⁇ ⁇ 25 cm) was used.
  • GILSON pump; master pump Model 305, slave pump Model 306, pump head 50SC, dynamic mixer Model 811D / A, pressure module Model 806, UV detector; UV-VIS detector Model 155, injector, fraction collector; Model 215, column: CHIRALPAK (registered trademark) AD-H, IA, IB, IC, ID, IE, IF manufactured by DAICEL, CHIRALCEL (registered trademark)
  • Optical rotation (+/ ⁇ ) was measured using a JASCO OR-2090 optical rotation detector (mercury xenon (Hg—Xe) lamp, 150 W) following fraction detection by a UV detector.
  • chromatography when there is a description of silica gel column chromatography, a parallel prep manufactured by YAMAZEN (column: Hi-Flash TM Column (Silicagel) manufactured by YAMAZEN, size; S (16 ⁇ 60 mm), M (20 ⁇ 75 mm) , L (26 ⁇ 100 mm), 2L (26 ⁇ 150 mm), 3L (46 ⁇ 130 mm)), or silica gel spherical PSQ 60B TM for chromatography manufactured by Fuji Silysia Chemical Co., Ltd., chromatography manufactured by Fuji Silysia Chemical Co., Ltd.
  • (+)-, (-)-, (R)-and (S)- are enantiomeric (+) form, (-) form, (R) -form and (S) —indicates isomer.
  • “*” in the steric configuration represents a relative configuration, and indicates any one enantiomer unless otherwise specified.
  • the organic layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium carbonate solution and saturated brine, dried over sodium sulfate, and filtered.
  • the solvent was distilled off under reduced pressure and dried under reduced pressure.
  • the residue was dissolved in acetonitrile (20 mL), Selectfluor TM (1.13 g, 3.19 mmol) was added at room temperature, and the mixture was stirred at room temperature for 11 hours, and then the solvent was evaporated under reduced pressure.
  • DCM was added to the residue to remove insolubles, and the solvent was evaporated under reduced pressure.
  • the organic layer was concentrated under reduced pressure, water was added to the residue, and ethyl acetate and 1N hydrochloric acid were added to separate the layers.
  • the aqueous layer was made alkaline with 2N aqueous sodium hydroxide solution and extracted with ethyl acetate.
  • the organic layer was dried over anhydrous sodium sulfate and filtered.
  • the solvent was distilled off under reduced pressure and dried to obtain the title compound (210 mg, 1.02 mmol).
  • the second optically active compound (S) (44 mg, 0.267 mmol; 98% ee) having a retention time of 44 minutes was obtained as a white solid.
  • ESI-MS m / z 307 [M + Na] + .
  • the organic layer was concentrated under reduced pressure, water was added to the residue, and ethyl acetate and 1N hydrochloric acid were added to separate the layers.
  • the aqueous layer was made alkaline with 2N aqueous sodium hydroxide solution and extracted with ethyl acetate.
  • the organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was distilled off under reduced pressure.
  • the second optically active compound (-) form (83 mg, 0.276 mmol; 96% ee) having a retention time of 49 minutes was obtained.
  • ESI-MS m / z 323 [M + Na] + .
  • the reaction mixture was concentrated under reduced pressure, ethyl acetate and water were added, and the separated aqueous layer was extracted twice with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure and dried to obtain the title compound (555 mg, 3.38 mmol).
  • the separated aqueous layer was extracted three times with diethyl ether, and the obtained organic layer was washed with saturated brine and dried over magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure. The resulting residue was dissolved in DMF (50 mL) and sodium azide (753 mg, 11.6 mmol) was added at room temperature. The reaction mixture was heated and stirred at 70 ° C. for 2 hours, then returned to room temperature, and water and diethyl ether were added. The separated aqueous layer was extracted three times with diethyl ether, and then the obtained organic layer was washed with water and saturated brine, and dried over magnesium sulfate.
  • the second optically active compound (S) having a retention time of 30 minutes (71 mg, 0.253 mmol; 98% ee) was obtained as a white solid.
  • Example 1 N- (benzo [b] thiophen-3-ylmethyl) sulfamide) of Patent Document 1 and Example 7 ((2S)-( ⁇ )-N- (6-chloro) of Patent Document 2 were used.
  • -2,3-dihydro-benzo [1,4] dioxin-2-ylmethyl) -sulfamide according to the production method of Patent Documents 1 and 2, respectively, as reference compounds (1,2) Using.
  • the compound was prepared in 0.45% methylcellulose-4.5% cremophor-10% dimethylsulfoxide aqueous solution to a dose volume of 10 ml / kg, and orally administered 1 hour before the hot plate test.
  • morphine was used, and as the negative control, only the above mixed solvent (Vehicle) containing no compound was used.
  • One mouse was placed on the hot plate one by one, and a stopwatch was immediately started to measure. The latency until the mouse showed escape behavior (licking the limbs or jumping away) was measured. In order to avoid excessive tissue damage, the cut-off time was 30 seconds, and the mouse was immediately removed from the measuring device after the measurement was completed. The results were expressed as mean ⁇ standard error.
  • Rat CCI model A rat CCI model was used to confirm the efficacy against chronic pain.
  • contact allodynia which is a typical symptom observed in patients with chronic pain, can be evaluated by using a response threshold to mechanical stimulation by von Frey filaments as an index (Bennett, GJ and Xie, Y). K., Pain, 33, p87-107, (1988)).
  • the rat CCI model was prepared according to the method of Bennett and Xie et al.
  • the sciatic nerve Under soflurane anesthesia, the sciatic nerve was exposed by opening the biceps femoris from the center of the thigh. The sciatic nerve was loosely squeezed four times with a silk suture (4-0) at intervals of about 1 mm, and then the biceps femoris and the skin were sutured. On day 14 after surgery, the effect of the compound on contact allodynia was evaluated. Prior to the test, the animals were placed in a measurement cage with a wire mesh floor and allowed to stand for about 30 minutes to acclimatize to changes in the environment, and then the measurement was started.
  • the compound was prepared in 0.45% methylcellulose-4.5% cremophor-10% dimethyl sulfoxide aqueous solution to a dose volume of 10 ml / kg and orally administered.
  • As a negative control only the above mixed solvent (vehicle) containing no compound was used.
  • the measurement of the response threshold to mechanical stimulation is performed according to the method of Chaplan et al. (Junal of Neuroscience Methods, 53 (1), p55-63 (1994)). Von Frey filaments (bending force: 0.4, 0.6, 1, 2, 4, 6, 8, 15 g) was used at the center of the hind limb. The free filament was pressed for about 6 seconds and the avoidance reaction was observed.
  • a 50% reaction threshold was produced according to Dixon's up-down method (Annual Review of Pharmacology and Toxicology, 20, p441-462 (1980)). The measurement was performed before drug administration and at 30, 90 and 4/180 time points after administration. The results were expressed as mean ⁇ standard error. Statistical analysis was performed using Two-way Repeated Measurements ANOVA and Dunnett-test, and p ⁇ 0.05 was judged as a statistically significant difference. ⁇ Result> The results of contact allodynia evaluation in the CCI model are shown in Table 7, Table 8, Table 9, and Table 10. Test compounds 1 and 2 showed a statistically significant analgesic effect at 50 mg / kg.
  • a magnet for detecting a change in the magnetic field was implanted subcutaneously in the left hind limb of the mouse under isoflurane anesthesia.
  • the compound was prepared in a 0.45% methylcellulose / 4.5% cremophor / 10% dimethylsulfoxide solution to a dose volume of 10 ml / kg and orally administered.
  • As a negative control only the above mixed solvent (vehicle) containing no compound was used.
  • gabapentin was intraperitoneally administered as a positive control.
  • a 2.5% formalin solution was prepared by diluting a formaldehyde solution (Wako Pure Chemical Industries) into physiological saline (Otsuka Pharmaceutical).

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PCT/JP2014/083374 2013-12-19 2014-12-17 １－インダンスルファミド誘導体を含む疼痛の治療および／または予防剤 Ceased WO2015093515A1 (ja)

Priority Applications (13)

Application Number Priority Date Filing Date Title
US15/102,046 US9610262B2 (en) 2013-12-19 2014-12-17 Therapeutic and/or preventive agent comprising 1-indansulfamide derivative for pain
ES14871860.4T ES2673876T3 (es) 2013-12-19 2014-12-17 Agente terapéutico y/o preventivo que comprende un derivado de 1-indansulfamida para el dolor
CA2932529A CA2932529C (en) 2013-12-19 2014-12-17 Therapeutic and/or preventive agent comprising 1-indansulfamide derivative for pain
KR1020167014850A KR102250214B1 (ko) 2013-12-19 2014-12-17 1-인단설파미드 유도체를 포함하는 통증에 대한 치료제 및/또는 예방제
BR112016012833-8A BR112016012833B1 (pt) 2013-12-19 2014-12-17 Agente terapêutico e/ou preventivo compreendendo derivado de 1-indansulfamida para dor
AU2014367781A AU2014367781B2 (en) 2013-12-19 2014-12-17 Therapeutic and/or preventive agent comprising 1-indansulfamide derivative for pain
EP14871860.4A EP3085369B1 (en) 2013-12-19 2014-12-17 Therapeutic and/or preventive agent comprising 1-indansulfamide derivative for pain
SG11201604484UA SG11201604484UA (en) 2013-12-19 2014-12-17 Therapeutic and/or preventive agent comprising 1-indansulfamide derivative for pain
RU2016122189A RU2678571C1 (ru) 2013-12-19 2014-12-17 Терапевтическое и/или профилактическое средство, содержащее производное 1-индансульфамида, против боли
MX2016007370A MX370898B (es) 2013-12-19 2014-12-17 Agente terapéutico y/o preventivo que comprende un derivado de 1-indansulfamida para el dolor.
JP2015553575A JP6518595B2 (ja) 2013-12-19 2014-12-17 １−インダンスルファミド誘導体を含む疼痛の治療および／または予防剤
CN201480066081.3A CN105792821B (zh) 2013-12-19 2014-12-17 包含1-茚满硫酰胺衍生物的疼痛治疗剂和/或预防剂
IL246036A IL246036B (en) 2013-12-19 2016-06-05 A therapeutic and/or prophylactic substance containing a derivative of 1-indensulfamide for pain

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KR102815521B1 (ko) 2022-11-11 2025-06-04 덕산에테르씨티 주식회사 내화성능 및 강도가 보강된 압력용기
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