ME00562B - Novi oblik soli pantoprazola - Google Patents
Novi oblik soli pantoprazolaInfo
- Publication number
- ME00562B ME00562B MEP-2008-847A MEP84708A ME00562B ME 00562 B ME00562 B ME 00562B ME P84708 A MEP84708 A ME P84708A ME 00562 B ME00562 B ME 00562B
- Authority
- ME
- Montenegro
- Prior art keywords
- pantoprazole
- magnesium dihydrate
- magnesium
- sodium sesquihydrate
- dihydrate
- Prior art date
Links
- 229960005019 pantoprazole Drugs 0.000 title claims abstract description 32
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 150000003839 salts Chemical group 0.000 title description 4
- RDRUTBCDIVCMMX-UHFFFAOYSA-N magnesium;5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Mg+2].COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC.COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC RDRUTBCDIVCMMX-UHFFFAOYSA-N 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 208000018556 stomach disease Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 159000000003 magnesium salts Chemical class 0.000 abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 10
- PWWDEIMGEBPTJL-UHFFFAOYSA-N 1-(pyridin-2-ylmethylsulfinyl)benzimidazole Chemical class C1=NC2=CC=CC=C2N1S(=O)CC1=CC=CC=N1 PWWDEIMGEBPTJL-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- YNWDKZIIWCEDEE-UHFFFAOYSA-N pantoprazole sodium Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC YNWDKZIIWCEDEE-UHFFFAOYSA-N 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- -1 4-methoxy-3, 5-dimethyl-2-pyridinyl Chemical group 0.000 description 3
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 2
- 229940091250 magnesium supplement Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960004048 pantoprazole sodium Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- PXVMLAJFILUEQV-UHFFFAOYSA-N 1-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2N(C3=CC=CC=C3N=2)OC(F)F)=C1OC PXVMLAJFILUEQV-UHFFFAOYSA-N 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 1
- 229960002337 magnesium chloride Drugs 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940050906 magnesium chloride hexahydrate Drugs 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- IKNCGYCHMGNBCP-UHFFFAOYSA-N propan-1-olate Chemical compound CCC[O-] IKNCGYCHMGNBCP-UHFFFAOYSA-N 0.000 description 1
- 229960004157 rabeprazole Drugs 0.000 description 1
- YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicinal Preparation (AREA)
- Drying Of Gases (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Detergent Compositions (AREA)
- Manufacture And Refinement Of Metals (AREA)
Abstract
Pronalazak se odnosi na dehidrat magnezijumove soli pantoprazola
Description
Predmet pronalaska
Ovaj pronalazak odnosi se na novi oblik soli aktivnog jedinjenja pantoprazola. Novi oblik soli može se koristiti u farmaceutskoj industriji za dobijanje medikamenata.
Stanje tehnike
Piridin-2-ilmetilsulfinil-1 H-benzimidazoli, kao što su opisani, na primer, u EP-A-0005129, EP-A-0166287, EP-A-0174726 i EP-A-0268956, usled svojih H*/K* ATPase-inhibirajućih dejstava, imaju znatnu važnost u terapiji bolesti koje potiču od povećanog lučenja želudačne kiseline. Primeri komercijalno dostupnih aktivnih jedinjenja iz ove grupe su 5-metoksi-2-[(4-metoksi-3, 5-dimetil-2-piridinil)metilsu! finil]-1H-benzimidazol (INN: omeprazol), 5-
difluorometoksi-2-[(3, 4-dimetoksi-2-piridinil)metilsulfinil]-1H-benzimidazol (INN: pantoprazol), 2-[3-metil-4-(2, 2, 2-trifluoroetoksi)-2-piridinil)metilsulfinil]-1H-benzimidazole (INN: lansoprazol) i 2-[4-(3-metoksipropoksi)-3-metilpiridin-2-il]metilsulfinil)-1 H-benzimidazol (INN: rabeprazol).
Zajednička osobina gore pomenutih piridin-2-ilmetilsulfinil-1 H-benzimidazola je osetljivost ovih aktivnih jedinjenja na kiselinu - koja je u krajnjoj instanci nezamenjiva zbog svoje efikasnosti - koja se očituje u njihovoj jakoj tendenciji da se rastvaraju u neutralnoj i, pogotovu kiseloj sredini, pri čemu se obrazuju produkti razgradnje koji su jako obojeni.
U prethodnom periodu, uprkos osetljivosti na kiselinu piridin2-ilmetilsulfinil-1 H-benzimidazola, ulagani su značajni napori da se dobiju stabilni oblici za oralnu administraciju koji su pogodni za lagerovanje koji sadrže piridin-2-ilmetilsulfinil-1 H-benzimidazole. Takvi oblici za oralnu administraciju stabilni i pogodni za lagerovanje (t. j. tablete ili kapsule) se sada mogu dobiti. Međutim dobijanje takvih oblika za oralnu administraciju relativno je komplikovano, i takođe se moraju preduzimati izvesne mere predostrožnosti u pogledu pakovanja, kako bi oblici za administraciju imali odgovarajuću stabilnost pri lagerovanju čak i pod ekstremnim uslovima lagerovanja (t. j. u tropima pri visokoj temperaturi i visokoj atmosferskoj vlažnosti).
Međunarodna patentna prijava WO97/41114 opisuje specifičan proces za dobijanje magnezijumovih soli piridin-2-ilmetilsulfinil-1 H-benzimidazola. Kao primer, takođe je među ostalim opisano dobijanje magnezijumove soli pantoprazola. Prema navedenim rezultatima analize, dobijena soje pantoprazol magnezijum u bezvodnom obliku.
Opis pronalaska
Sada je pronađeno da dihidrat magnezijumove soli pantoprazola ima veoma iznenađujuća svojstva stabilnosti, koja čine da izgleda naročito pogodan za upotrebu u čvrstim oblicima ili oblicima pogodnim za oralnu administraciju. On pokazuje vrlo značajno poboljšane osobine stabilnosti i u odnosu na sam pantoprazol i u poređenju sa pantoprazol natrijum seskvihidratom (oblik aktivnog jedinjenja koji se nalazi na tržištu od 1994, Evropski patent 0 589 981), ili u poredjenju sa pantoprazol natrijum monohidratom (intermedijarni oblik koji se koristi u industrijskom dobijanju, Evropski patent 0 533 790).
Tako je pantoprazol magnezijum dihidrat potpuno stabilan u toku 4 dana na 90 °C i ne pokazuje gotovo nikakvu promenu boje ili razgradnju, dok pantoprazol natrijum seskvihidrat i monohidrat za isto vreme postaju mrko-crveni uz obrazovanje značajnih količina produkata razgradnje.
Pronalazak se prema tome odnosi na dihidrat magnezijumove soli pantoprazola (pantoprazol magnezijum dihidrat).
Pantoprazol magnezijum dihidrat može da se koristi za lečenje i prevenciju svih bolesti za koje se smatra da se mogu lečiti ili sprečavati upotrebom piridin-2-ilmetilsulfinil-1H-benzimidazola. Naročito, pantoprazol magnezijum dihidrat može da se koristi u lečenju stomačnih poremećaja.
Zbog svojih osobina rastvorljivosti, shvatljive su mogućnosti primene pantoprazol magnezijum dihidrata jer je za ostvarenje istih moralo do sada da se pribegava određenim farmaceutskim preparatima. Tako je, među ostalim, upotreba pantoprazol magnezijum dihidrata naročito pogodna tamo gde aktivno jedinjenje treba da se oslobađa i apsorbuje tokom relativno dugog perioda (pogledati, na primer, Evropsku patentnu prijavu 0 841 903). Pomoću kombinacije magnezijumove soli pantoprazola sa natrijumovom soli, moguće je postići traženi rastvor za izvesne željene nivoe aktivne supstance u krvi.
Pantoprazol magnezijum dihidrat se dobija na poznat način reakcijom pantoprazola ili lako rastvorljive soli pantoprazola (t. j. natrijum pantoprazola) sa magnezijumovom soli u vodi ili u smešama vode sa polarnim organskim rastvaračima (t. j. alkoholima, poželjno etanolom ili izopropanolom, ili ketonima, na primer acetonom ili butanonom).
Pogodne magnezijumove soli koje se mogu koristiti prema postupku su, na primer, magnezijum hlorid, bromid, fluorid, jodid, formijat, acetat, propionat, sulfat, glukonat ili karbonat. Alkoksidi magnezijuma (na primer magnezijum metoksid, etoksid, (izo)propoksid, butoksid, heksoksid ili fenoksid), ili magnezijum hidroksid mogu takođe da reaguju sa pantoprazolom ili natrijum pantoprazolom u vodenoj sredini.
Primer
Magnezijum bisf5-[difiuorometoksfl-2-fr3, 4-dimetoksi-2-pindintPmetinsulfinin-1H-benzimi-dazolidldihidrat
3, 85 kg (8. 9 mola) pantoprazol Na seskvihidrata [natrijum [5-[đifluorometoksi]-2-[[3, 4-dimetQksi-2-piridinil]metil]sulfinil]-1H-benzimidazolid]seskvihidrata] rastvoreno je na 20-25 °C u 38, 5 I prečišćene vode u sudu za mešanje Rastvor 1, 0 kg (4, 90 mala) magnezijum dihlorid heksahidrata u 8 I prečišćene vode dodaje se uz mešanje na 20-30 °C u toku 3 do 4 sata Posle mešanja u toku daljih 18 sati, istaložena čvrsta materija se iscentrifugira, ispere sa 23 I prečišćene vode, mesa na 20-30 °C u toku 1 do 2 sata u 35 I prečišćene vode, ponovo centrifugira i opet ispere sa 30-50 I prečišćene vode. Čvrsti proizvod se osuši na 50°C u vakuumu (30-50 mbar) dok se ne postigne da preostali sadržaj vode ne iznosi < 4, 8%. Proizvod se tada samelje
Naslovno jedinjenje se dobije u obliku praha bele do bež boje, koje se u daljem farmaceutskom postupku neposredno upotrebljava
Dobitak 3, 40 kg (90% teoretskog); sadržaj vode: 4, 5-4, 6%; tačka topljenja: 194-196 °C uz razgradnju.
Alternativno, naslovno jedinjenje se može dobiti koristeći mesavine organskih rastvarača sa vodom Za to se pantoprazol Na seskvihidrat rastvori u organskom rastvaraču na 50-60 °C. Ekvivalenti 0, 5 mola magnezijumove soli (t. j. magnezijum hlorid heksahidrat), rastvoreni u vodi dodaju se kap po kap, i rastvor se pusti da se ohladi uz mešanje. Ta istaložena čvrsta materija se odfiltrira, ispere sa odgovarajućim organskim rastvaračem i osuši u vakuumu na 50 °C do konstantne težine Naslovno jedinjenje se dobije u obfiku bezbojnog praha Primeri za različite rastvarače dati su u tabeli 1.
Tabela 1:
Alternativno, naslovno jedinjenje se može dobiti reagovanjem pantoprazola sa baznom magnezijumovom soli kao što je magnezijum metilat, na primer na sledeći način: 90 g pantoprazola se rastvori u 700 ml 2-propanola na 60-70 °C. Doda se 13, 4 g (0, 5 mola) čvrstog magnezijuma metilata i rastvor se pusti da se ohladi uz mešanje i filtrira se. Posle dodavanja 36 ml vode obrazovana čvrsta kristalna materija se odfiltrira, ispere sa vodom i osuši u vakuumu na 50 °C do konstantne težine. Naslovno jedinjenje sa tačkom topljenja 194-196°C (sadržaj vode 4, 8 %) dobije se u obliku čvrste materije bež boje.
Claims (8)
1. Pantoprazol magnezijum dihidrat.
2. Medikament kojeg čini pantoprazol magnezijum dihidrat sa uobičajenim pomoćnim sastojcima.
3. Pantoprazol magnezijum dihidrat za upotrebu u lečenju poremećaja stomaka ili probavnog trakta.
4. Kombinacija medikamenta kojeg čini pantoprazol magnezijum dihidrat i pantoprazol natrijum seskvihidrat.
5. Kombinovani medikament kojeg čini pantoprazol magnezijum dihidrat i pantoprazo natrijum seskvihidrat u težinskom odnosu (u odnosu na pantoprazol) od 10% pantoprazol magnezijum dihidrata i 90% pantoprazol natrijum seskvihidrata do 90% pantoprazol magnezijum dihidrata i 10% pantoprazol natrijum seskvihidrata.
6. Kombinovani medikament kojeg čine pantoprazol magnezijum dihidrat i pantoprazol natrijum seskvihidrat u težinskom odnosu (u odnosu na pantoprazol) od 25% pantoprazol magnezijum dihidrata i 75% pantoprazol natrijum seskvihidrata do 75% pantoprazol magnezijum dihidrata i 25% pantoprazol natrijum seskvihidrata.
7. Kombinovani medikament kojeg čine pantoprazol magnezijum dihidrat i pantoprazol natrijum seskvihidrat u težinskom odnosu (u odnosu na pantoprazol) od 40% pantoprazol magnezijum dihidrata i 60% pantoprazol natrijum seskvihidrata do 60% pantoprazol magnezijum dihidrata i 40% pantoprazol natrijum seskvihidrata.
8. Kombinovani medikament kojeg čine pantoprazol magnezijum dihidrat i pantoprazol natrijum seskvihidrat u težinskom odnosu (u odnosu na pantoprazol) od 50% pantoprazol magnezijum dihidrata i 50% pantoprazol natrijum seskvihidrata.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843413A DE19843413C1 (de) | 1998-08-18 | 1998-08-18 | Neue Salzform von Pantoprazol |
| PCT/EP1999/005928 WO2000010995A1 (en) | 1998-08-18 | 1999-08-12 | Novel salt form of pantoprazole |
| YUP-113/01A RS50071B (sr) | 1998-08-18 | 1999-08-12 | Novi oblik soli pantoprazola |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ME00562B true ME00562B (me) | 2011-12-20 |
| ME00562A ME00562A (en) | 2011-12-20 |
Family
ID=7881823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-847/08A ME00562A (en) | 1998-08-18 | 1999-08-12 | Novel salt form of pantoprazole |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US6410569B1 (me) |
| EP (1) | EP1105386B1 (me) |
| JP (1) | JP2002523411A (me) |
| KR (1) | KR100657835B1 (me) |
| CN (1) | CN1146558C (me) |
| AT (1) | ATE219074T1 (me) |
| AU (1) | AU761715B2 (me) |
| BG (1) | BG65255B1 (me) |
| BR (1) | BR9914288A (me) |
| CA (1) | CA2341031C (me) |
| CZ (1) | CZ293734B6 (me) |
| DE (3) | DE19843413C1 (me) |
| DK (1) | DK1105386T3 (me) |
| EA (1) | EA004431B1 (me) |
| EE (1) | EE04278B1 (me) |
| ES (1) | ES2178896T3 (me) |
| HR (1) | HRP20010117B1 (me) |
| HU (1) | HU226618B1 (me) |
| IL (3) | IL141328A0 (me) |
| ME (1) | ME00562A (me) |
| MX (1) | MXPA01001758A (me) |
| NO (1) | NO319782B1 (me) |
| NZ (1) | NZ509761A (me) |
| PL (1) | PL198801B1 (me) |
| PT (1) | PT1105386E (me) |
| RS (1) | RS50071B (me) |
| SI (1) | SI1105386T1 (me) |
| SK (1) | SK285105B6 (me) |
| TR (1) | TR200100287T2 (me) |
| UA (1) | UA58605C2 (me) |
| WO (1) | WO2000010995A1 (me) |
| ZA (1) | ZA200100934B (me) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19843413C1 (de) * | 1998-08-18 | 2000-03-30 | Byk Gulden Lomberg Chem Fab | Neue Salzform von Pantoprazol |
| MY137726A (en) | 2000-11-22 | 2009-03-31 | Nycomed Gmbh | Freeze-dried pantoprazole preparation and pantoprazole injection |
| DE10234617B4 (de) * | 2002-07-29 | 2013-04-04 | Nycomed Gmbh | Neues Salz von (S)-Pantoprazol |
| TW200410955A (en) * | 2002-07-29 | 2004-07-01 | Altana Pharma Ag | Novel salt of (S)-PANTOPRAZOLE |
| US7507829B2 (en) | 2002-12-19 | 2009-03-24 | Teva Pharmaceuticals Industries, Ltd | Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates |
| US20060235053A1 (en) * | 2003-05-06 | 2006-10-19 | Atlanta Pharma Ag | Agents for the treatment of lower abdominal disorders |
| CL2004000983A1 (es) * | 2003-05-08 | 2005-03-04 | Altana Pharma Ag | Composicion farmaceutica oral en forma de tableta que comprende a pantoprazol magnetico dihidratado, en donde la forma de tableta esta compuesto por un nucleo, una capa intermedia y una capa exterior; y uso de la composicion farmaceutica en ulceras y |
| PE20050150A1 (es) * | 2003-05-08 | 2005-03-22 | Altana Pharma Ag | Una forma de dosificacion que contiene (s)-pantoprazol como ingrediente activo |
| CN1791406A (zh) * | 2003-05-19 | 2006-06-21 | 普利瓦研究与发展有限公司 | 5－(二氟甲氧基)－2－[[(3,4－二甲氧基－2－吡啶基)甲基]亚硫酰基]－1h－苯并咪唑(泮托拉唑)钠水络合物的固态形式 |
| US7683177B2 (en) * | 2003-06-10 | 2010-03-23 | Teva Pharmaceutical Industries Ltd | Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole |
| WO2005012289A1 (en) * | 2003-07-17 | 2005-02-10 | Altana Pharma Ag | Novel salt of (r) - pantoprazole |
| ATE386522T1 (de) * | 2003-07-23 | 2008-03-15 | Nycomed Gmbh | Alkalisalze von protonenpumpen-hemmern |
| CN100457104C (zh) * | 2003-07-23 | 2009-02-04 | 尼科梅德有限责任公司 | 质子泵抑制剂的碱性盐 |
| WO2005074930A1 (en) * | 2004-01-28 | 2005-08-18 | Altana Pharma Ag | Pharmaceutical combinations of (s) -pantoprazole with nsaid or corticosteroids |
| WO2005074932A1 (en) * | 2004-01-28 | 2005-08-18 | Altana Pharma Ag | The use of (s) - pantoprazole magnesium for the treatment of airway disorders |
| WO2005074898A2 (en) * | 2004-01-28 | 2005-08-18 | Altana Pharma Ag | Composition comprising (s) pantoprazole and an antibiotic for treating helicobacter pylori |
| WO2005074931A1 (en) * | 2004-01-28 | 2005-08-18 | Altana Pharma Ag | Pharmaceutical combinations comprising (s) -pantoprazole |
| EP1711179A2 (en) * | 2004-01-28 | 2006-10-18 | Altana Pharma AG | Calcium, potassium, zinc, lithium and aluminium salts of pantoprazole and (s)-pantoprazole |
| EP1716136A1 (en) * | 2004-02-11 | 2006-11-02 | Ulkar Kimya Sanayii Ve Ticaret A.S. | Pyridine benzimidazole sulfoxides of high purity |
| WO2005082888A1 (en) * | 2004-03-01 | 2005-09-09 | Milen Merkez Ilac Endustrisi A.S. | Process for the preparation of magnesium salt of omeprazole |
| PT1746980E (pt) * | 2004-05-07 | 2012-01-25 | Nycomed Gmbh | Forma de dosagem farmacêutica compreendendo granulados assim como o seu processo de fabrico |
| WO2007041790A1 (en) * | 2005-10-14 | 2007-04-19 | Jon Pty Limited | Salts of proton pump inhibitors and process for preparing same |
| EP1954691A2 (en) | 2006-06-12 | 2008-08-13 | Teva Pharmaceutical Industries Ltd | Amorphous and crystalline forms of pantoprazole magnesium salt |
| EP1960388A1 (en) * | 2006-11-06 | 2008-08-27 | Teva Pharmaceutical Industries Ltd. | Processes for preparing substantially pure pantoprazole magnesium |
| EP3187494A1 (en) * | 2015-12-30 | 2017-07-05 | KRKA, tovarna zdravil, d.d., Novo mesto | Process for the preparation of pantoprazole sodium sesquihydrate |
| SI3397630T1 (sl) * | 2015-12-30 | 2021-11-30 | Krka, tovarna zdravil, d.d., Novo mesto, | Postoek za pripravo natrijevega pantoprazolata seskvihidrata |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE7804231L (sv) * | 1978-04-14 | 1979-10-15 | Haessle Ab | Magsyrasekretionsmedel |
| IL75400A (en) * | 1984-06-16 | 1988-10-31 | Byk Gulden Lomberg Chem Fab | Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same |
| JPS6150978A (ja) * | 1984-08-16 | 1986-03-13 | Takeda Chem Ind Ltd | ピリジン誘導体およびその製造法 |
| FI90544C (fi) * | 1986-11-13 | 1994-02-25 | Eisai Co Ltd | Menetelmä lääkeaineina käyttökelpoisten 2-pyridin-2-yyli-metyylitio- ja sulfinyyli-1H-bensimidatsolijohdannaisten valmistamiseksi |
| DE4018642C2 (de) * | 1990-06-11 | 1993-11-25 | Byk Gulden Lomberg Chem Fab | Neue Salzform des 5-Difluormethoxy-2-[(3,4-dimethoxy-2-pyridyl) methylsulfinyl]-1H-benzimitazol-Natriumsalzes |
| YU48263B (sh) * | 1991-06-17 | 1997-09-30 | Byk Gulden Lomberg Chemische Fabrik Gmbh. | Postupak za dobijanje farmaceutskog preparata na bazi pantoprazola |
| SE9302396D0 (sv) | 1993-07-09 | 1993-07-09 | Ab Astra | A novel compound form |
| SE9600070D0 (sv) * | 1996-01-08 | 1996-01-08 | Astra Ab | New oral pharmaceutical dosage forms |
| SE508669C2 (sv) * | 1996-04-26 | 1998-10-26 | Astra Ab | Nytt förfarande |
| DE19843413C1 (de) * | 1998-08-18 | 2000-03-30 | Byk Gulden Lomberg Chem Fab | Neue Salzform von Pantoprazol |
-
1998
- 1998-08-18 DE DE19843413A patent/DE19843413C1/de not_active Expired - Fee Related
-
1999
- 1999-08-12 CN CNB998098000A patent/CN1146558C/zh not_active Expired - Fee Related
- 1999-08-12 HR HR20010117A patent/HRP20010117B1/xx not_active IP Right Cessation
- 1999-08-12 DK DK99941605T patent/DK1105386T3/da active
- 1999-08-12 EE EEP200100054A patent/EE04278B1/xx unknown
- 1999-08-12 WO PCT/EP1999/005928 patent/WO2000010995A1/en not_active Ceased
- 1999-08-12 HU HU0103257A patent/HU226618B1/hu not_active IP Right Cessation
- 1999-08-12 PL PL345993A patent/PL198801B1/pl unknown
- 1999-08-12 AT AT99941605T patent/ATE219074T1/de active
- 1999-08-12 JP JP2000566268A patent/JP2002523411A/ja active Pending
- 1999-08-12 AU AU55156/99A patent/AU761715B2/en not_active Ceased
- 1999-08-12 PT PT99941605T patent/PT1105386E/pt unknown
- 1999-08-12 RS YUP-113/01A patent/RS50071B/sr unknown
- 1999-08-12 NZ NZ509761A patent/NZ509761A/en not_active IP Right Cessation
- 1999-08-12 BR BR9914288-0A patent/BR9914288A/pt not_active Application Discontinuation
- 1999-08-12 EA EA200100208A patent/EA004431B1/ru not_active IP Right Cessation
- 1999-08-12 SK SK236-2001A patent/SK285105B6/sk not_active IP Right Cessation
- 1999-08-12 KR KR1020017001911A patent/KR100657835B1/ko not_active Expired - Lifetime
- 1999-08-12 SI SI9930096T patent/SI1105386T1/xx unknown
- 1999-08-12 MX MXPA01001758A patent/MXPA01001758A/es active IP Right Grant
- 1999-08-12 CA CA002341031A patent/CA2341031C/en not_active Expired - Lifetime
- 1999-08-12 IL IL14132899A patent/IL141328A0/xx unknown
- 1999-08-12 EP EP99941605A patent/EP1105386B1/en not_active Expired - Lifetime
- 1999-08-12 ME MEP-847/08A patent/ME00562A/xx unknown
- 1999-08-12 DE DE1999601840 patent/DE122005000049I2/de active Active
- 1999-08-12 TR TR2001/00287T patent/TR200100287T2/xx unknown
- 1999-08-12 US US09/762,303 patent/US6410569B1/en not_active Expired - Lifetime
- 1999-08-12 CZ CZ2001621A patent/CZ293734B6/cs not_active IP Right Cessation
- 1999-08-12 DE DE69901840T patent/DE69901840T2/de not_active Expired - Lifetime
- 1999-08-12 IL IL14115799A patent/IL141157A0/xx active IP Right Grant
- 1999-08-12 ES ES99941605T patent/ES2178896T3/es not_active Expired - Lifetime
- 1999-12-08 UA UA2001021133A patent/UA58605C2/uk unknown
-
2001
- 2001-01-23 BG BG105173A patent/BG65255B1/bg unknown
- 2001-01-29 IL IL141157A patent/IL141157A/en not_active IP Right Cessation
- 2001-02-02 ZA ZA200100934A patent/ZA200100934B/en unknown
- 2001-02-12 NO NO20010718A patent/NO319782B1/no not_active IP Right Cessation
-
2002
- 2002-05-01 US US10/135,528 patent/US6686379B2/en not_active Expired - Lifetime
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