CA2190185A1 - Polymorphs a and b of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl) propyl]piperazine - Google Patents
Polymorphs a and b of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl) propyl]piperazineInfo
- Publication number
- CA2190185A1 CA2190185A1 CA002190185A CA2190185A CA2190185A1 CA 2190185 A1 CA2190185 A1 CA 2190185A1 CA 002190185 A CA002190185 A CA 002190185A CA 2190185 A CA2190185 A CA 2190185A CA 2190185 A1 CA2190185 A1 CA 2190185A1
- Authority
- CA
- Canada
- Prior art keywords
- piperazine
- polymorph
- dioxolan
- propyl
- diphenylmethyl
- 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.)
- Abandoned
Links
- LRMJAFKKJLRDLE-UHFFFAOYSA-N dotarizine Chemical compound O1CCOC1(C=1C=CC=CC=1)CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 LRMJAFKKJLRDLE-UHFFFAOYSA-N 0.000 title claims description 20
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 208000012886 Vertigo Diseases 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 231100000889 vertigo Toxicity 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 229950005624 dotarizine Drugs 0.000 description 15
- CBQYNPHHHJTCJS-UHFFFAOYSA-N Alline Chemical compound C1=CC=C2C3(O)CCN(C)C3NC2=C1 CBQYNPHHHJTCJS-UHFFFAOYSA-N 0.000 description 4
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000646 scanning calorimetry Methods 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical class C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Two polymorphs A and B of 1-(diphenylmethyl)-4-¢3-(2-phenyl-1,3-dioxolan-2-yl)pr opyl!piperazine have been identified. A process for producing both polymorphs and the subsequent use thereof are also disclosed.
Description
2i90185 S POLYMORPE~S A AND B QF 1- (DIPHENYLMETHYL) -4- [3 - (2 -PHENYL-l. 3 -DIOXOI,A~- 2 - YL) PROPYL] PIPERAZINE
The presel~t illvention relates to novel Polymorplls A and B oE 1- (Di~henylmetllyl) -4- [3- (2-pllenyl-1,3-dioxolan-2-yl) propyl]piperazine -compound known as dotarizine (WTiO).
Brief de8cril~tion of the drawinq8 Fig~lre ] i~ an infrared (IR) spectrnm Oe dotarizine Polymorp~l ~ at t:lle range rom 4000 to 400 cm~.
Figure 2 is an infrared (IR) spectrum of dotarizine Polymorph ~ at t}le range from 2000 ~o 400 cm~.
Figllr~ 3 is a di f ~erential scanning calorimetry (DSC) t~lermogram of dotarizine Polymorp~
Figure 4 is an X-ray powder difEractogram of dotarizine Pol ymo rph 7~ .
Figure 5 is an infrared (IR) spectrum of dotarizine Polymorph B at tlle range from 4000 to 400 cm~.
Figure ~ is an infrared (IR) spectrum of dotarizine Polymorph B at tlle range from 2000 to 400 cm~.
Figure 7 is a differential scanning calorimetry (DSC) t~lermogram of dotarizine Polymorph B.
Figure 3 is an X-ray powder difEractogram of dotarizine Polymorph B.
Detailed de~c!rlDtion of the inyen~ion 1- (Diphenylmetilyl) -4- [3- (2-phenyl- 1,3-dioxolan-2-yl) propyl~piperazine is an antiserotonergic agent (5HT~C and 5HT2) and calcium antagonist. Tllis compound is efrective in ~lle prophylaxis of migraine and i n tlle treatment of vertigo .
The preparation of thi.s compound was di8closed ill European Pa~ellt No. 0097340 s}lowillg a meltirlg point of 93-97~C. Tlle app].;.cants have foulld out that dotari.zille exhibits two novel polymorpJIs, A and B, whicil llave a melting point irl the range between 100 and 103~C. The difEererltial scanning calorimetry (DSC) tllermograms of both polymorphs do not show significant differences as ill~lstrated in Figures 3 and 7. Neverthele8s, ~lle applicant8 llave found out tllat their IR spectra do silow sigl~i~icant dif~erences especially in the range 1100-900 cm~
in accordance Wit~l t~le enlarged IR spectra in Figures 2 and 6. Dotarizine polymorpil A is characterized by s~lowing bands at 2962, 2949, 2808, 2767, 1446, 1040, 1025, 1002, 993, 970, 960, 761 and 707 cm' and dot~rizine polymorp~l B i8 cllaracterized by s~lowing bands at 2961, 2883, 2812, Z777, 2760, 1~}8, 1283, 1058, 1042, 1029, 1006, 978, 951, 758 and 703 cm' (Figures 1 and 5). The present invention provides a process for obtainirlg selectively both polymorphs of dotarizine; polymorph A is o~tained by crystallization in metlla~lol, wlli]e polymorpll B is obtained by crystallization in n - hexalle .
Tlle use of polymorpll 7~ for preparing pharmaceutical rormulations in t~le form of drops (suspensions) is ... . . .. . .
3 2~ 93~85 recommended, while the use of polymorph B or preparing capsul es or otller solid ~orms is pre~erred.
Polymorplls )~ and B oE dotarizille mixed witl pllarmaceutically acceptable carriers can be administered at daily doses ranging from 50 and 150 mg.
Tlle ollowing exampl es wi.ll illustrate the preparation of polymorphs 1~ and B o~ dotarizille and pharmaceutical ~orm~llations containing t~lem. T~le examples are not intended to limitate the scope of the invention as defined ~lereinabove or as claimed hereinater.
Exam~le PolymorphAof 1- (diphenylmethyl) -4- [3- (2-phenyl-1,3-dioxolan -2-yl)propyl)piperazine 11. 2 g of dotarizine are dissolved in 56 ml o methanol at re~lux. The solution is 3~iltered and allowed to crystallize at a temperature of between 20 and 25C witll gentle stirring.
1~ crys~alline solid is formed, which weighs 9.9 g (yield 88.59~) ater dried.
R spectrum (Ksr), range from 4000 to 400 cm': Figure 1.
IR spectrum (KBr), range ~rom 2000 to 400 cm-': Figure 2.
Di~erential scanning calorimetry (OSC) thermogram:
Flgure 3.
X-ray powder diractogram: Figure 4.
2~9Q18~
Examb 1 e Polymorph~of 1- (diphenylmethyl) -4- [3- (2-pherlyl-1,3-dioxolan -2-yl)propyl)piperazine 10 g of dotarizine are dissolved in 100 ml of n-hexane at reFlux. Tlle 801ution is ~iltered and allowed to crystallize at a temperat~lre of between 20 and 25~C with stirring. A
cry~t:alline solid i9 eormed, wllich weig}ls 7.6 g (yield 76~) af ~er dried 10 IR 8pectrum (KBr), range from 4000 to 400 cm': Figure 5.
IR spectrum (KBr), range ~rom 2000 to 400 cm~: Figure 6.
Di~erential scanning calorimetry (DSC) ~lermogram:
Figure 7.
X-ray powder diffractogram: Figure 8.
ExamDle 3 Drop~
Composition for 100 ml:
Dotarizine polymorp}l 7~.. .......... 7 . 50 g 20Sucrose............................ 30 . 00 g Microcrystalline cellulose RC-581.. 1.00 g Carboxymetllylcellulose sodium..... O.lo g Saccharin sodium................... 3 . 50 g Methyl -p-hydroxybenzoate.......... 0.15 g 25Propyl-p-hydroxybenzoate........... 0.03 g Polysorbate 80 .................... 0 . 20 g Di stilled water q. 8 . ........... 100 . 00 ml ~xamDle 3 Cap3ule3 Composition ~or 1 capsule Dotarizine polymorph ~3 .... 50 . O mg 5Silicon dioxide ............ 2.0 mg Croscarmellose sodium....... 8.0 mg Corn starch .. .. . 50 . 0 mg Talc ......... ................. .. 8 . o mg Magl~esium stearate . .. 1. 5 mg 10 Microcrystalline cellulose q. 8 .. 210 . 0 mg
The presel~t illvention relates to novel Polymorplls A and B oE 1- (Di~henylmetllyl) -4- [3- (2-pllenyl-1,3-dioxolan-2-yl) propyl]piperazine -compound known as dotarizine (WTiO).
Brief de8cril~tion of the drawinq8 Fig~lre ] i~ an infrared (IR) spectrnm Oe dotarizine Polymorp~l ~ at t:lle range rom 4000 to 400 cm~.
Figure 2 is an infrared (IR) spectrum of dotarizine Polymorph ~ at t}le range from 2000 ~o 400 cm~.
Figllr~ 3 is a di f ~erential scanning calorimetry (DSC) t~lermogram of dotarizine Polymorp~
Figure 4 is an X-ray powder difEractogram of dotarizine Pol ymo rph 7~ .
Figure 5 is an infrared (IR) spectrum of dotarizine Polymorph B at tlle range from 4000 to 400 cm~.
Figure ~ is an infrared (IR) spectrum of dotarizine Polymorph B at tlle range from 2000 to 400 cm~.
Figure 7 is a differential scanning calorimetry (DSC) t~lermogram of dotarizine Polymorph B.
Figure 3 is an X-ray powder difEractogram of dotarizine Polymorph B.
Detailed de~c!rlDtion of the inyen~ion 1- (Diphenylmetilyl) -4- [3- (2-phenyl- 1,3-dioxolan-2-yl) propyl~piperazine is an antiserotonergic agent (5HT~C and 5HT2) and calcium antagonist. Tllis compound is efrective in ~lle prophylaxis of migraine and i n tlle treatment of vertigo .
The preparation of thi.s compound was di8closed ill European Pa~ellt No. 0097340 s}lowillg a meltirlg point of 93-97~C. Tlle app].;.cants have foulld out that dotari.zille exhibits two novel polymorpJIs, A and B, whicil llave a melting point irl the range between 100 and 103~C. The difEererltial scanning calorimetry (DSC) tllermograms of both polymorphs do not show significant differences as ill~lstrated in Figures 3 and 7. Neverthele8s, ~lle applicant8 llave found out tllat their IR spectra do silow sigl~i~icant dif~erences especially in the range 1100-900 cm~
in accordance Wit~l t~le enlarged IR spectra in Figures 2 and 6. Dotarizine polymorpil A is characterized by s~lowing bands at 2962, 2949, 2808, 2767, 1446, 1040, 1025, 1002, 993, 970, 960, 761 and 707 cm' and dot~rizine polymorp~l B i8 cllaracterized by s~lowing bands at 2961, 2883, 2812, Z777, 2760, 1~}8, 1283, 1058, 1042, 1029, 1006, 978, 951, 758 and 703 cm' (Figures 1 and 5). The present invention provides a process for obtainirlg selectively both polymorphs of dotarizine; polymorph A is o~tained by crystallization in metlla~lol, wlli]e polymorpll B is obtained by crystallization in n - hexalle .
Tlle use of polymorpll 7~ for preparing pharmaceutical rormulations in t~le form of drops (suspensions) is ... . . .. . .
3 2~ 93~85 recommended, while the use of polymorph B or preparing capsul es or otller solid ~orms is pre~erred.
Polymorplls )~ and B oE dotarizille mixed witl pllarmaceutically acceptable carriers can be administered at daily doses ranging from 50 and 150 mg.
Tlle ollowing exampl es wi.ll illustrate the preparation of polymorphs 1~ and B o~ dotarizille and pharmaceutical ~orm~llations containing t~lem. T~le examples are not intended to limitate the scope of the invention as defined ~lereinabove or as claimed hereinater.
Exam~le PolymorphAof 1- (diphenylmethyl) -4- [3- (2-phenyl-1,3-dioxolan -2-yl)propyl)piperazine 11. 2 g of dotarizine are dissolved in 56 ml o methanol at re~lux. The solution is 3~iltered and allowed to crystallize at a temperature of between 20 and 25C witll gentle stirring.
1~ crys~alline solid is formed, which weighs 9.9 g (yield 88.59~) ater dried.
R spectrum (Ksr), range from 4000 to 400 cm': Figure 1.
IR spectrum (KBr), range ~rom 2000 to 400 cm-': Figure 2.
Di~erential scanning calorimetry (OSC) thermogram:
Flgure 3.
X-ray powder diractogram: Figure 4.
2~9Q18~
Examb 1 e Polymorph~of 1- (diphenylmethyl) -4- [3- (2-pherlyl-1,3-dioxolan -2-yl)propyl)piperazine 10 g of dotarizine are dissolved in 100 ml of n-hexane at reFlux. Tlle 801ution is ~iltered and allowed to crystallize at a temperat~lre of between 20 and 25~C with stirring. A
cry~t:alline solid i9 eormed, wllich weig}ls 7.6 g (yield 76~) af ~er dried 10 IR 8pectrum (KBr), range from 4000 to 400 cm': Figure 5.
IR spectrum (KBr), range ~rom 2000 to 400 cm~: Figure 6.
Di~erential scanning calorimetry (DSC) ~lermogram:
Figure 7.
X-ray powder diffractogram: Figure 8.
ExamDle 3 Drop~
Composition for 100 ml:
Dotarizine polymorp}l 7~.. .......... 7 . 50 g 20Sucrose............................ 30 . 00 g Microcrystalline cellulose RC-581.. 1.00 g Carboxymetllylcellulose sodium..... O.lo g Saccharin sodium................... 3 . 50 g Methyl -p-hydroxybenzoate.......... 0.15 g 25Propyl-p-hydroxybenzoate........... 0.03 g Polysorbate 80 .................... 0 . 20 g Di stilled water q. 8 . ........... 100 . 00 ml ~xamDle 3 Cap3ule3 Composition ~or 1 capsule Dotarizine polymorph ~3 .... 50 . O mg 5Silicon dioxide ............ 2.0 mg Croscarmellose sodium....... 8.0 mg Corn starch .. .. . 50 . 0 mg Talc ......... ................. .. 8 . o mg Magl~esium stearate . .. 1. 5 mg 10 Microcrystalline cellulose q. 8 .. 210 . 0 mg
Claims (6)
1 and 2.
2) - Polymorph B of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl)propyl]piperazine characterized in that it shows IR bands at 2961, 2883, 2812, 2777, 2760, 1448, 1283, 1058, 1042, 1029, 1006, 978, 951, 758 and 703 cm-1 as presented in Figures 5 and 6.
3) - A process for the preparation of Polymorph A of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl))propyl]
piperazine by crystallization in methanol.
piperazine by crystallization in methanol.
4) - A process for the preparation of Polymorph B of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl)propyl]
piperazine by crystallization in n-hexane.
5) - A pharmaceutical composition containing the polymorph and pharmaceutically acceptable carriers according to claims 1 and 3, which is useful in the prophylaxis of migraine and in the treatment of vertigo.
6) - A pharmaceutical composition containing the polymorph and pharmaceutically acceptable carriers according to claims 2 and 4, which is useful in the prophylaxis of migraine and in the treatment of vertigo.
7) - A method for the prophylaxis of migraine and the treatment of vertigo consisting in treating patients with an effective amount of the compound according to claims 1, 3 and
piperazine by crystallization in n-hexane.
5) - A pharmaceutical composition containing the polymorph and pharmaceutically acceptable carriers according to claims 1 and 3, which is useful in the prophylaxis of migraine and in the treatment of vertigo.
6) - A pharmaceutical composition containing the polymorph and pharmaceutically acceptable carriers according to claims 2 and 4, which is useful in the prophylaxis of migraine and in the treatment of vertigo.
7) - A method for the prophylaxis of migraine and the treatment of vertigo consisting in treating patients with an effective amount of the compound according to claims 1, 3 and
5 in order to relieve them from such conditions.
8) - A method for the prophylaxis of migraine and the treatment of vertigo consisting in treating patients with an effective amount of the compound according to claims 2, 4 and
8) - A method for the prophylaxis of migraine and the treatment of vertigo consisting in treating patients with an effective amount of the compound according to claims 2, 4 and
6 in order to relieve them from such conditions.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002190185A CA2190185A1 (en) | 1995-03-28 | 1995-03-28 | Polymorphs a and b of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl) propyl]piperazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002190185A CA2190185A1 (en) | 1995-03-28 | 1995-03-28 | Polymorphs a and b of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl) propyl]piperazine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2190185A1 true CA2190185A1 (en) | 1996-10-03 |
Family
ID=4159242
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002190185A Abandoned CA2190185A1 (en) | 1995-03-28 | 1995-03-28 | Polymorphs a and b of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl) propyl]piperazine |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2190185A1 (en) |
-
1995
- 1995-03-28 CA CA002190185A patent/CA2190185A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8921375B2 (en) | Polymorphic forms of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride | |
| RU2081116C1 (en) | 5-(2-4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6- -chloro-1,3-dihydro-2h-indol-2-one hydrochloride monohydrate and process for preparation thereof | |
| US7981897B2 (en) | Crystal form of (3-cyano-1H-Indo1-7-yl)-[4-(4-fluorophenethyl)piperazin-1-yl]methanone, hydrochloride | |
| EA025438B1 (en) | CRYSTALLINE COMPLEX OF 1-CYANO-2-(4-CYCLOPROPYL-BENZYL)-4-(β-D-GLUCOPYRANOS-1-YL)BENZENE, METHODS FOR ITS PREPARATION AND THE USE THEREOF FOR PREPARING MEDICAMENTSCRYSTALLINE COMPLEX OF 1-CYANO-2-(4-CYCLOPROPYL-BENZYL)-4-(β-D-GLUCOPYRANOS-1-YL)BENZENE, METHODS FOR ITS PREPARATION AND THE USE THEREOF FOR PREPARING MEDICAMENTS | |
| CZ63799A3 (en) | Spirocyclic metalloprotease inhibitors | |
| EP0768302A2 (en) | Hydroxypyridinones | |
| CN108101780B (en) | Flurbiprofen chalcone compounds, preparation method and application thereof | |
| CA2479924C (en) | Purified lasofoxifene and a method for purification of racemic lasofoxifene by recrystallization | |
| CA2190185A1 (en) | Polymorphs a and b of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl) propyl]piperazine | |
| CA2164296C (en) | Heterocyclic chemistry | |
| US5852021A (en) | Polymorph B of 1-(diphenylmethyl)-4- 3-(2-phenyl-1,3-dioxolan-2-YL) propyl! piperazine | |
| WO2006115285A1 (en) | Pharmaceutical composition | |
| MXPA03005884A (en) | Amlodipine hemimaleate. | |
| HU199814B (en) | Process for producing benzothiazinone derivatives and pharmaceutical compositions comprising such active ingredient | |
| SK13622000A3 (en) | Crystalline form of paroxetine | |
| US4545936A (en) | Novel aminonaphthacene derivatives and process for preparation thereof | |
| JP4664634B2 (en) | Novel benzamidine derivatives or salts thereof | |
| EP0821673B1 (en) | New form of (e)-3- 6- (2,6-dichlorophenyl)-thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-2-propenoic acid | |
| WO2018153546A1 (en) | Tetrahydropyran and tetrahydrothiopyran methanone derivatives having multimodal activity against pain | |
| NZ282827A (en) | Polymorphs of 1-(diphenylmethyl)-4-[3-(2-phenyl-1,3-dioxolan-2-yl) propyl] piperazine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |