WO2015170827A1 - Procédé de production d'un cristal de silodosine de forme gamma - Google Patents
Procédé de production d'un cristal de silodosine de forme gamma Download PDFInfo
- Publication number
- WO2015170827A1 WO2015170827A1 PCT/KR2015/003252 KR2015003252W WO2015170827A1 WO 2015170827 A1 WO2015170827 A1 WO 2015170827A1 KR 2015003252 W KR2015003252 W KR 2015003252W WO 2015170827 A1 WO2015170827 A1 WO 2015170827A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- silodosin
- crystals
- crystal
- formula
- type
- Prior art date
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 78
- PNCPYILNMDWPEY-QGZVFWFLSA-N silodosin Chemical compound N([C@@H](CC=1C=C(C=2N(CCCO)CCC=2C=1)C(N)=O)C)CCOC1=CC=CC=C1OCC(F)(F)F PNCPYILNMDWPEY-QGZVFWFLSA-N 0.000 title claims abstract description 61
- 229960004953 silodosin Drugs 0.000 title claims abstract description 61
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- 238000010899 nucleation Methods 0.000 claims description 6
- 239000001294 propane Substances 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 5
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 12
- 230000008901 benefit Effects 0.000 abstract description 3
- 238000002425 crystallisation Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 8
- 239000012046 mixed solvent Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000001273 butane Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 2
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 2
- 238000000113 differential scanning calorimetry Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241001506137 Rapa Species 0.000 description 1
- 208000028938 Urination disease Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229960004205 carbidopa Drugs 0.000 description 1
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- VJECBOKJABCYMF-UHFFFAOYSA-N doxazosin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 VJECBOKJABCYMF-UHFFFAOYSA-N 0.000 description 1
- 238000007905 drug manufacturing Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000012395 formulation development Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- -1 hydroxypropyl Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 238000002647 laser therapy Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011471 prostatectomy Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000007704 transition Effects 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
Definitions
- the present invention relates to a method for producing gamma-type crystals of silodosin safely and efficiently.
- Prostatic hyperplasia is a high frequency disease in elderly men. 70% of men in their 60s suffer from the disease. Recently, as aging accelerates, the number of patients with prostatic hyperplasia is increasing rapidly, and interest in its treatment is also increasing.
- the main treatment methods for prostatic hyperplasia include pharmacotherapy and surgery. Surgical treatments include laparotomy, transurethral prostatectomy (TUR-P), high temperature therapy, laser therapy, and stent placement.
- TUR-P transurethral prostatectomy
- As pharmacotherapy ⁇ -adrenergic receptor blocking drugs, anti-androgen drugs, herbal medicines and the like are known.
- si lodosin one of the ⁇ ⁇ adrenergic receptor antagonists
- Polymorphism refers to a phenomenon in which two or more crystalline forms are formed for a single compound. Although the same compounds have different crystalline forms, they show differences in water mechanical properties such as solubility, melting point and stability. In general, amorphous forms are often unsuitable for use in medicine because they have high solubility but low stability and high hygroscopic properties. On the other hand, crystalline forms have relatively low solubility problems but have high stability and low hygroscopicity. It has an advantage. Therefore, in the case of raw drug products, if there is no problem in solubility, it is preferable to prepare a crystalline form.
- Crystals characterized by the principal peaks of 2 ⁇ equal to 7.0 ⁇ 0.2 ° , 12.5 ⁇ 0 2 ° , 18.5 ⁇ 0.2 °, 19.5 ⁇ 0.2 °, 20.7 ⁇ 0.2 °, and 21.1 ⁇ 0.2 ° ); And (3) Crystals characterized by the principal peaks of 2 ⁇ being 6.0 ⁇ 0.2 °, 10.6 ⁇ 0.2 °, 12.6 ⁇ 0.2 ° , 17.1 ⁇ 0.2 ° , 17.9 ⁇ 0.2 ° , 20.7 ⁇ 0.2 ° and 23.7 ⁇ 0.2 ° called ⁇ -type crystals).
- the ⁇ -type crystals may be prepared by recrystallization of crude crystals using ethyl acetate, ethyl formate, acetone, methyl ethyl ketone, acetonitrile, tetrahydrofuran, acetone / acetonitrile (1: 1) mixed solvent, and the like.
- ⁇ -type crystals can be prepared by dissolving crude crystals in an appropriate amount of methanol, and then petroleum ether and shaking them vigorously to precipitate crystals. : 4)
- the disclosed ⁇ -form crystal is due to the volume of the crystallization solvent, the nature of the production process size to obtain a required capacity of the production equipment it is difficult to determine certain disadvantages ⁇ 'i.
- it is easy to form homogeneous crystals with low volume of crystallization solvent but since the use of toluene as the crystallization solvent, long drying time is required to remove high boiling point of luluene below the standard of 890PPII1 (ICH guideline). There is a problem that it is necessary and difficult to completely remove the residual solvent.
- X-type crystals can be obtained only by using luluene as the crystallization solvent, and thus, it is highly likely that luluene remains in the active ingredient of pharmaceuticals, meeting the market expectations for high purity and high quality raw materials. There is a problem that cannot be done. Therefore, if the problem is solved, other properties having excellent properties similar to those of ⁇ -type crystals
- the crystalline form can be used in pharmaceuticals, there is an advantage that can be selected in the formulation development process suitable for the finished drug manufacturing process.
- EP 2474529 discloses the crystal forms of syldoscin ( ⁇ type) and the 2 ⁇ of 3.1, 4.8, 6.28.9 and 2 ⁇ having main peaks of 6.6, 10.5, 13.1, 21.3 and 22.8 in powder X-ray diffraction patterns.
- the crystal form of epsilonsin (epsilon form) which has a major peak of 11.6, is disclosed.
- the epsilon form crystal has improved solubility compared with the three existing crystal forms.
- the equilibrium concentration difference after 60 minutes is not very large, and in case of stability, it refers to the transition between crystalline forms, and does not mention the change in purity through stability test.
- the present inventors have developed a method for producing a silodosin Y-type crystal using alcohol and a seed, which has been studied for a safer and more efficient method for producing a silodosin ⁇ -type crystal.
- SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a method for safely and efficiently producing a silodosin Y crystal.
- the present invention comprises the steps of (1) dissolving silodosin in an alcohol solvent; (2) seeding the silodosin ⁇ type crystal while precipitating the solution to precipitate the crystal; And (3) filtering and drying the precipitated crystals, to provide a method for producing a silodosin Y-type crystal.
- the production method of the silodosin Y crystal according to the present invention is safe because it does not use toluene, which is harmful to the human body, and the amount of alcohol used in the preparation is relatively small. Therefore, it is not only suitable for mass production and environmentally friendly, but also capable of producing products of constant quality and homogeneous crystals.
- 1 is a graph showing the results of X-ray diffraction analysis (XRD) of the silodosin ⁇ -type crystal of the formula (1) according to the present invention.
- FIG. 2 is a graph showing the differential scanning calorimetry (DSC) results of the silodosin ⁇ -type crystal of Formula 1 according to the present invention.
- DSC differential scanning calorimetry
- the method for producing a silodosin ⁇ -type crystallization method comprises the steps of: (1) dissolving silodosin in alcohol; (2) seeding the silodosin ⁇ -type crystal while precipitating the solution to precipitate the crystal; And (3) filtering and drying the precipitated crystals.
- the starting material silodosin may be a silodosin crude crystal or crystal.
- examples of the alcohol solvent for dissolving the silodosin include ethane,
- 2-propane may be used.
- the solvent may be used in an amount of 0.5 to 100 mL, preferably in an amount of 3 to 30 mL, based on 1 g of silodosin of Formula 1, which is a starting material.
- the amount of solvent described above should be used in an amount of 100 mL or less based on l g of silodosin to prevent a decrease in yield.
- dissolution of the silodosin can be carried out in a temperature range of 30 ° C to 100 ° C, preferably 40 ° C to 80 ° C.
- step (2) crystallization is performed by seeding the silodosin ⁇ -type crystal while subjecting the solution of the step (1).
- the crystallization may be carried out at -20 to 40 ° C, preferably 0 to 30 ° C, more preferably 10 to 20 ° C, it should be carried out at 40 ° C or less to prevent yield reduction.
- the crystallization may be carried out at the above-mentioned temperature for 0.5 hours to 48 hours, preferably 1 hour to 24 hours.
- the silodosin ⁇ -type crystals seeding for crystallization are commercially available or prepared by other methods, from 0.01 to 50 g, preferably 1, based on 100 g of the starting material silodosin. To 10 g.
- the precipitated crystals are filtered and dried. The filtration and drying can be carried out according to methods well known in the pharmaceutical art.
- Example 1 Preparation of ⁇ -type Crystals of Silodosin (Formula 1) After 2-propanol (100 mL) was added to silodosin (10.Og; Formula 1; Hanmi Fine Chemical), the mixture was heated to 50 ° C. and dissolved. . The solution was slowly angled to 20 ° C. and seeded with silodosin Y-type crystals (0.3 g) (Hanmi Chemical), followed by stirring at 3 ° C. and 5 ° C. for 2 hours at the same temperature. The resulting solid was filtered, washed with 2-propanol (10 mL) and dried to give white silodosin ⁇ type crystals (8.3 g, 80%; Formula 1).
- the structure of the silodosin was analyzed using a nuclear magnetic resonance spectrum (NMR) 400 ⁇ z FT-NMR Spectrometer (Varian, 400-MR).
- Example 2 Preparation of ⁇ -type crystals of silodosin (Formula 1) After adding 1-butanol (100 mL) to silodosin (10.Og; Formula 1), the mixture was heated to 45 ° C. and dissolved. It was. The solution was slowly angled to 20 ° C. and seeded with silodosin ⁇ -type crystals (0.5 g), followed by stirring at 3 ° C. and 5 ° C. for 2 hours at the same temperature.
- Example 3 Preparation of ⁇ -type crystals of silodosin (Formula 1) 2-butanol (100 mL) was added to silodosin (10. Og; Formula 1), and then dissolved by heating at 45 ° C. The solution was slowly decanted with 2 (rc and seeded with silodosin ⁇ -type crystals (0,5 g) and stirred for 3 hours at the same temperature and 2 hours at 5 ° C.
- Example 4 Preparation of ⁇ -type crystals of silodosin (Formula 1) To propane (10. Og; Formula 1), 2-propane and a mixed solvent of 2-butanol (1: 1; 140 mL) were added, and then dissolved by raising the temperature to 40 ° C. The solution was washed with 20 ° C. After cooling slowly and seeding the silodosin ⁇ -type crystals (0.3 g), the mixture was stirred at the same temperature for 3 hours at 2 ° C.
- Example 6 Preparation of ⁇ -type crystals of silodosin (Formula 1) After t-butane (120 mL) was added to silodosin (lO.Og; Formula 1), the solution was dissolved by heating at 40 ° C. The solution was slowly angled to 20 ° C. and seeded with silodosin ⁇ -type crystals (0.3 g), followed by stirring at the same temperature for 3 hours.
- XRD X-ray diffraction analysis
- DSC differential scanning calorimetry
- METLER TOLEDO differential scanning calorimeter
Abstract
La présente invention concerne un procédé de production d'un cristal de silodosine de forme γ, et le procédé de production d'un cristal de silodosine de forme γ selon la présente invention présente les avantages d'être sans risque du fait de la non utilisation de toluène, qui est nocif pour le corps humain ; d'être adapté à la production de masse et respectueux de l'environnement étant donné que la quantité d'alcool utilisée dans la production est relativement faible ; et d'être susceptible de produire un produit de qualité uniforme et un cristal homogène.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020140054634A KR20150127996A (ko) | 2014-05-08 | 2014-05-08 | 실로도신 감마형 결정의 제조방법 |
KR10-2014-0054634 | 2014-05-08 |
Publications (1)
Publication Number | Publication Date |
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WO2015170827A1 true WO2015170827A1 (fr) | 2015-11-12 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/KR2015/003252 WO2015170827A1 (fr) | 2014-05-08 | 2015-04-01 | Procédé de production d'un cristal de silodosine de forme gamma |
Country Status (2)
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KR (1) | KR20150127996A (fr) |
WO (1) | WO2015170827A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR101673160B1 (ko) * | 2014-10-24 | 2016-11-07 | 보령제약 주식회사 | 실로도신 γ 결정형의 제조방법 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004022538A1 (fr) * | 2002-09-06 | 2004-03-18 | Kissei Pharmaceutical Co., Ltd. | Cristal pour medicament solide a administration orale et medicament solide a administration orale destine au traitement de la dysurie contenant ce cristal |
US7834193B2 (en) * | 2004-10-27 | 2010-11-16 | Kissei Pharmaceutical Co., Ltd. | Indoline compound and process for producing the same |
WO2012077138A1 (fr) * | 2010-12-09 | 2012-06-14 | Panacea Biotec Limited | Procédés de cristallisation du (r)-1-(3-hydroxypropyl)-5-[2-[2-(2,2,2- trifluoroéthoxy)phénoxy]éthylamino]propyl]indoline-7-carboxamide |
WO2015093456A1 (fr) * | 2013-12-17 | 2015-06-25 | 東和薬品株式会社 | Cristal de silodosine de forme γ et son procédé de production |
-
2014
- 2014-05-08 KR KR1020140054634A patent/KR20150127996A/ko not_active Application Discontinuation
-
2015
- 2015-04-01 WO PCT/KR2015/003252 patent/WO2015170827A1/fr active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004022538A1 (fr) * | 2002-09-06 | 2004-03-18 | Kissei Pharmaceutical Co., Ltd. | Cristal pour medicament solide a administration orale et medicament solide a administration orale destine au traitement de la dysurie contenant ce cristal |
US7834193B2 (en) * | 2004-10-27 | 2010-11-16 | Kissei Pharmaceutical Co., Ltd. | Indoline compound and process for producing the same |
WO2012077138A1 (fr) * | 2010-12-09 | 2012-06-14 | Panacea Biotec Limited | Procédés de cristallisation du (r)-1-(3-hydroxypropyl)-5-[2-[2-(2,2,2- trifluoroéthoxy)phénoxy]éthylamino]propyl]indoline-7-carboxamide |
WO2015093456A1 (fr) * | 2013-12-17 | 2015-06-25 | 東和薬品株式会社 | Cristal de silodosine de forme γ et son procédé de production |
Also Published As
Publication number | Publication date |
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KR20150127996A (ko) | 2015-11-18 |
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