CS228523B2 - Process for the production of nasal powder form with increased resorpability and alkaloid content of type ergot peptides - Google Patents
Process for the production of nasal powder form with increased resorpability and alkaloid content of type ergot peptides Download PDFInfo
- Publication number
- CS228523B2 CS228523B2 CS817502A CS750281A CS228523B2 CS 228523 B2 CS228523 B2 CS 228523B2 CS 817502 A CS817502 A CS 817502A CS 750281 A CS750281 A CS 750281A CS 228523 B2 CS228523 B2 CS 228523B2
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- Czechoslovakia
- Prior art keywords
- hydrogen
- methyl
- hydrogen atom
- isopropyl
- formula
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- 238000000034 method Methods 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 229930013930 alkaloid Natural products 0.000 title claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 title description 2
- 108090000765 processed proteins & peptides Proteins 0.000 title description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 title 1
- 229940052404 nasal powder Drugs 0.000 title 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 13
- 239000001257 hydrogen Substances 0.000 claims abstract 13
- 229910052736 halogen Chemical group 0.000 claims abstract 2
- 150000002367 halogens Chemical group 0.000 claims abstract 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 10
- 239000008101 lactose Substances 0.000 claims description 9
- 239000007903 gelatin capsule Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 239000011248 coating agent Substances 0.000 claims 1
- 238000000576 coating method Methods 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 229960004318 dihydroergocristine Drugs 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 230000002685 pulmonary effect Effects 0.000 abstract 2
- LIMAOLZSWRJOMG-HJPBWRTMSA-N dihydroergocristine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@H]1CN(C)[C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C(C)C)C1=CC=CC=C1 LIMAOLZSWRJOMG-HJPBWRTMSA-N 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 210000001331 nose Anatomy 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 description 2
- 229960004704 dihydroergotamine Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000002850 nasal mucosa Anatomy 0.000 description 2
- QHZUABXEBRGBLP-LKWYKXIFSA-N (6aR,9R,10aR)-N-[(2R,4R,9aS,9bR)-4-benzyl-9b-hydroxy-3,5-dioxo-2-propan-2-yl-3a,4,7,8,9,9a-hexahydrofuro[3,2-g]indolizin-2-yl]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide (6aR,9R,10aR)-N-[(2R,4R,9aS,9bR)-9b-hydroxy-3,5-dioxo-2,4-di(propan-2-yl)-3a,4,7,8,9,9a-hexahydrofuro[3,2-g]indolizin-2-yl]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide (6aR,10aR)-N-[(2S,4S,9bS)-9b-hydroxy-4-(2-methylpropyl)-3,5-dioxo-2-propan-2-yl-3a,4,7,8,9,9a-hexahydrofuro[3,2-g]indolizin-2-yl]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.CS(O)(=O)=O.C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)C4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)C(C)C)C(C)C)=C3C2=CNC3=C1.C1=CC([C@H]2CC(CN(C)[C@@H]2C2)C(=O)N[C@@]3(C(=O)C4[C@@H](C(N5CCCC5[C@@]4(O)O3)=O)CC(C)C)C(C)C)=C3C2=CNC3=C1.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(C21)=O)(NC(=O)[C@H]1CN(C)[C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C(C)C)C1=CC=CC=C1 QHZUABXEBRGBLP-LKWYKXIFSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- -1 alkyl radical Chemical class 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229940069063 dihydro-beta-ergocryptine Drugs 0.000 description 1
- SEALOBQTUQIVGU-QNIJNHAOSA-N dihydroergocornine Chemical compound C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)C(C)C)C(C)C)=C3C2=CNC3=C1 SEALOBQTUQIVGU-QNIJNHAOSA-N 0.000 description 1
- 229960004290 dihydroergocornine Drugs 0.000 description 1
- DEQITUUQPICUMR-HJPBWRTMSA-N dihydroergocristine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@H]1CN(C)[C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C(C)C)C1=CC=CC=C1 DEQITUUQPICUMR-HJPBWRTMSA-N 0.000 description 1
- ADYPXRFPBQGGAH-UMYZUSPBSA-N dihydroergotamine mesylate Chemical compound CS(O)(=O)=O.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C)C1=CC=CC=C1 ADYPXRFPBQGGAH-UMYZUSPBSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- SBFXHXZNBNFPHV-PXXBSISHSA-N epicriptine Chemical compound C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)[C@H](C)CC)C(C)C)=C3C2=CNC3=C1 SBFXHXZNBNFPHV-PXXBSISHSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- XJSMBWUHHJFJFV-VTIMJTGVSA-N α-dihydroergocryptine Chemical compound C([C@H]1N(C)C2)C([C]34)=CN=C4C=CC=C3[C@H]1C[C@H]2C(=O)N[C@@]1(C(C)C)C(=O)N2[C@@H](CC(C)C)C(=O)N3CCC[C@H]3[C@]2(O)O1 XJSMBWUHHJFJFV-VTIMJTGVSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- 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
- A61K9/0043—Nose
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01D—MEASURING NOT SPECIALLY ADAPTED FOR A SPECIFIC VARIABLE; ARRANGEMENTS FOR MEASURING TWO OR MORE VARIABLES NOT COVERED IN A SINGLE OTHER SUBCLASS; TARIFF METERING APPARATUS; MEASURING OR TESTING NOT OTHERWISE PROVIDED FOR
- G01D2207/00—Indexing scheme relating to details of indicating measuring values
- G01D2207/10—Displays which are primarily used in aircraft or display aircraft-specific information
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Předmětem vynálezu je způsob výroby nazální práškovité aplikační formy se zvýšenou resorbovatelností s obsahem alkaloidů typu ergotových peptidů obecného vzorce I
kde
Ri znamená atom vodíku nebo atom halogenu,
Ra znamená atom vodíku nebo alkylový zbytek o 1 až 4 atomech uhlíku a buď
i) R3 znamená isopropyl, sekundární butyl nebo· isobutyl,
Ri znamená methyl, ethyl nebo isopropyl,
Rs znamená atom vodíku a
R6 znamená atom vodíku nebo methoxyskupinu, nebo spolu tvoří Rs a Rs další vazbu, nebo ii) R3 znamená benzyl,
Ri znamená methyl,
Rs znamená atom vodíku a
R6 znamená atom vodíku nebo methoxyskupinu,
Vyznačující se tím, že se sloučeniny obecného vzorce I zpracují na mikronizovanou formu o velikosti částic menší než 10 μη a pak se spolu s mikronizovanou laktózou plní do vhodného obalu při poměru sloučeniny ·obecného vzorce I k laktóze · 0,25 až
12,5 % k 99,75 až 87,5 %.
Vhodné lékové formy je možno připravit běžným způsobem. Přesné složení bude samozřejmě záviset především na použité účinné látce a na nosiči nebo ředidle. Sloučeniny mohou mít velikost částic až 10 μη · v průměru, s výhodou 0,5 až 5 μΐη. Nosičem nebo· ředidlem je zejména laktóza, která může tvořit 87,5 až 97,5 % celkové hmotnosti · přípravku v tvrdé želatinové kapsli, například k · použití jakýmkoli vhodným přístrojem, jako je gumový balónek a podobně.
Očinné látky obecného vzorce I se tedy podávají do nosu v práškovité formě.
Aplikátorem · může být jakýkoli běžný aplikátor pro nanášení prášku do nosu, například upravený inhalační přístroj pro podávání práškovitých léčiv.
Účinná látka má být přítomna v mikro228523 mízované formě, například s průměrem nižším než 10 /tm, například 2 až 10 μπι spolu s mikronizovanou nebo nemikronizovanou laktózou. Hmotnostní poměr účinné látky k laktóze může být 0,25 : 12,5 °/o až 99,75 : : 87,5 °/o. Tuto směs je možno plnit do· tvrdých želatinových .. kapslí po 20 až 40 mg do jedné kapsle a užívat běžným způsobem.
Takto získaným farmaceutickým prostředkem je možno ošetřovat nosní sliznici místním způsobem.
V případě, že v obecném vzorci I znamená Rž alkylovou skupinu, jde s výhodou o methylovou nebo isopropylovou skupinu. V případě, že Ri znamená atom halogenu, jde o atom fluoru, chloru, bromu nebo jodu, s výhodou bromu.
Výhodnými sloučeninami obecného vzorce I jsou dihydroergokristin, a- nebo @-dihydroergokryptin, dihydroergokornin, které se s výhodou užívají ve formě směsi, známé jako dihydroergotoxin, bromkryptin, dihydroergotamin a dihydroergonin. Sloučeniny obecného vzorce I je možno· užít ve volné formě nebo jako adiční soli s kyselinami, například jako methansulfonáty, maleáty nebo tartráty.
Bylo prokázáno, že v případě, že se tyto prostředky nanášely v práškovité formě na sliznici nosu u opic, anestetizováných fencyklidinem, došlo k podstatnému zvýšení koncentrace uvedených látek v krvi obvykle s velmi krátkým nástupem této koncentrace při použití například 1 až 10 mg této sloučeniny. Koncentraci účinných látek v krvi je možno měřit běžným radioimunologickým způsobem, například způsobem, uvedeným v publikaci J. Rosennhaler a H. Munzer, Experientia 32, 234 (1976).
Svrchu uvedené zkoušky prokázaly, že vhodnou dávkou sloučenin obecného vzorce I je 0,1 až 10 mg, sloučeniny je možno podávat 1- až 5krát denně podle potřeby.
Vynález bude osvětlen následujícím příkladem.
P říkl ad
Aplikátor pro podání dihydroergotaminu ve formě prášku
Směs mikronizovaného dihydroergotaminmethansulfonátu s mikronizovanou laktózou se plní do želatinové kapsle.
Obsah se aplikuje do· nosu ve formě spraye, například gumovým balónkem.
Claims (4)
- PŘEDMĚT VYNALEZU1. Způsob výroby nazální práškovité aplikační formy se zvýšenou resorbovatelností s obsahem alkaloidů typu argotových peptidů obecného vzorce I kdeRl . znamená atom vodíku nebo atom halogenu,Rz znamená . atom vodíku nebo· alkylový zbytek o 1 až 4 atomech uhlíku a buďi) R3 znamená isopropyl, sekundární butyl nebo· isobutyl,Rl · znamená · methyl, ethyl nebo isopropyl,Rs· znamená atom vodíku aR6 znamená atom vodíku nebo methoxyskupinu, nebo· spolu tvoří Rs a R6 další vazbu, nebo ii) R3 znamená benzyl,Rl znamená methyl,Rs znamená atom vodíku aRe znamená atom vodíku nebo methoxyskupinu, vyznačující se tím, že se sloučeniny obecného vzorce I zpracují na mikronizovanou formu o velikosti částic menší než 10 μτη a pak se spolu s mikronizovanou laktózou plní do· vhodného obalu při poměru sloučeniny obecného· vzorce I k laktóze 0,25 až12,5 % k 99,75 až 87,5 %.
- 2. Způsob podle bodu 1, vyznačující se tím, že se užije sloučenina obecného vzorce I, v níž Ri, Rs a Re znamenají atomy vodíku, Rž a Ri znamenají methylové zbytky a R3 znamená benzylovou skupinu.
- 3. Způsob podle bodu 1, vyznačující se tím, že se užije sloučenina obecného- · vzorce I, v níž Ri znamená atom vodíku nebo atom halogenu, Rz znamená atom vodíku nebo alkylový zbytek o 1 až 4 atomech uhlíku s výjimkou terc.butylové skupiny, R3 znamená isopropyl, sek.butyl, isobutyl nebo benzyl, Ri znamená methyl, ethyl nebo isopropyl, Rs znamená atom vodíku a Re znamená atom vodíku nebo methoxyskupinu nebo spolu Rs a R6 tvoří další vazbu za předpokladu, že v případě, že současně R3 znamená benzyl, R4 methyl a Ri · atom vodíku, má alespoň jeden ze substituentů Rs a Re význam odlišný od atomu vodíku.
- 4. Způsob podle bodu 1, vyznačující se tím, že se sloučenina obecného· vzorce I plní spolu s mikronizovanou laktózou do kapsle z tvrdé želatiny. .
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1457576 | 1976-11-19 | ||
| CH698977 | 1977-06-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS228523B2 true CS228523B2 (en) | 1984-05-14 |
Family
ID=25700540
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS777615A CS228502B2 (en) | 1976-11-19 | 1977-11-18 | Method for the production of an application form with increased resorpability containing alkaloide |
| CS817502A CS228523B2 (en) | 1976-11-19 | 1977-11-18 | Process for the production of nasal powder form with increased resorpability and alkaloid content of type ergot peptides |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS777615A CS228502B2 (en) | 1976-11-19 | 1977-11-18 | Method for the production of an application form with increased resorpability containing alkaloide |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US4462983A (cs) |
| JP (1) | JPS5366440A (cs) |
| AT (1) | AT368881B (cs) |
| AU (1) | AU520754B2 (cs) |
| CA (1) | CA1103585A (cs) |
| CS (2) | CS228502B2 (cs) |
| CY (1) | CY1266A (cs) |
| DE (2) | DE2750090A1 (cs) |
| DK (1) | DK153440C (cs) |
| ES (1) | ES464275A1 (cs) |
| FI (1) | FI773376A7 (cs) |
| FR (1) | FR2371454A1 (cs) |
| GB (1) | GB1592563A (cs) |
| GR (1) | GR65229B (cs) |
| HK (1) | HK85984A (cs) |
| HU (1) | HU185924B (cs) |
| IE (1) | IE46167B1 (cs) |
| IL (1) | IL53419A (cs) |
| KE (1) | KE3453A (cs) |
| MY (1) | MY8400055A (cs) |
| NL (1) | NL187892C (cs) |
| NO (1) | NO773839L (cs) |
| NZ (1) | NZ185711A (cs) |
| PH (1) | PH23643A (cs) |
| PT (1) | PT67292B (cs) |
| SE (1) | SE451944B (cs) |
| SG (1) | SG61784G (cs) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2750090A1 (de) * | 1976-11-19 | 1978-06-01 | Sandoz Ag | Neue verabreichungsformen fuer organische verbindungen |
| US4284648A (en) * | 1979-08-03 | 1981-08-18 | The University Of Kentucky Research Foundation | Nasal administration of propranolol |
| CH649300A5 (de) * | 1981-08-07 | 1985-05-15 | Sandoz Ag | Ergopeptinderivate, ihre herstellung und verwendung. |
| FI81258C (fi) * | 1982-02-01 | 1990-10-10 | Sandoz Ag | Foerfarande foer framstaellning av en farmaceutisk komposition foer nasal administration. |
| GB8301659D0 (en) * | 1983-01-21 | 1983-02-23 | Leo Ab | Smoking substitutes |
| GB8413795D0 (en) * | 1984-05-30 | 1984-07-04 | Sandoz Ltd | Organic compounds |
| GB8426922D0 (en) * | 1984-10-24 | 1984-11-28 | Sandoz Ltd | Galenic formulation |
| GB8501015D0 (en) * | 1985-01-16 | 1985-02-20 | Riker Laboratories Inc | Drug |
| FR2628638B1 (fr) * | 1985-03-06 | 1992-12-18 | Sandoz Lab | Dispositif de pulverisation par voie nasale d'une dose unitaire de medicament en solution |
| JPS61263918A (ja) * | 1985-05-16 | 1986-11-21 | Banyu Pharmaceut Co Ltd | 経皮吸収用製剤 |
| JPS63500175A (ja) * | 1985-05-22 | 1988-01-21 | リポソ−ム テクノロジ−，インコ−ポレイテツド | リポソ−ム吸入法および吸入システム |
| CA1291036C (en) * | 1986-04-23 | 1991-10-22 | Edwin I. Stoltz | Nasal administration of drugs |
| US4782047A (en) * | 1986-05-22 | 1988-11-01 | Syntex Pharmaceuticals International Ltd. | Aqueous steroid formulations for nasal administration |
| US4897256A (en) * | 1986-11-25 | 1990-01-30 | Abbott Laboratories | LHRH analog formulations |
| DE3710216A1 (de) * | 1987-03-27 | 1988-10-06 | Rentschler Arzneimittel | Verwendung von dihydroergotamin und seinen salzen zur lokalen behandlung trophischer stoerungen |
| DE68915203T2 (de) * | 1988-03-22 | 1994-09-22 | Fisons Plc, Ipswich, Suffolk | Pharmazeutische Mischungen. |
| US4929640A (en) * | 1988-04-04 | 1990-05-29 | George D. McAdory | Medicaments intended for combined use in the improvement of lymphocyte function |
| GB2237510B (en) * | 1989-11-04 | 1993-09-15 | Danbiosyst Uk | Small particle drug compositions for nasal administration |
| IT1247472B (it) * | 1991-05-31 | 1994-12-17 | Fidia Spa | Processo per la preparazione di microsfere contenenti componenti biologicamente attivi. |
| AU659328B2 (en) * | 1992-06-12 | 1995-05-11 | Teijin Limited | Ultrafine powder for inhalation and production thereof |
| ATE204750T1 (de) * | 1992-06-12 | 2001-09-15 | Teijin Ltd | Pharmazeutische zubereitung zur anwendung in den atemwegen |
| DE69434304T2 (de) * | 1993-03-26 | 2005-12-29 | Merkus, Franciscus Wilhelmus H.M. | Pharmazeutische Zusammensetzungen zur intranasalen Verabreichung von Dihydroergotamin |
| US6632456B1 (en) | 1993-06-24 | 2003-10-14 | Astrazeneca Ab | Compositions for inhalation |
| US5830853A (en) | 1994-06-23 | 1998-11-03 | Astra Aktiebolag | Systemic administration of a therapeutic preparation |
| US6794357B1 (en) * | 1993-06-24 | 2004-09-21 | Astrazeneca Ab | Compositions for inhalation |
| US20010003739A1 (en) * | 1993-06-24 | 2001-06-14 | Astrazeneca Ab | Systemic administration of a therapeutic preparation |
| JP4155594B2 (ja) | 1994-12-22 | 2008-09-24 | アストラゼネカ・アクチエボラーグ | エアゾール製剤 |
| EE9700136A (et) * | 1994-12-22 | 1997-12-15 | Astra Aktiebolag | Paratüroidhormooni PTH sisaldav ravimpreparaat inhaleerimiseks |
| SE9404468D0 (sv) * | 1994-12-22 | 1994-12-22 | Astra Ab | Powder formulations |
| US6524557B1 (en) * | 1994-12-22 | 2003-02-25 | Astrazeneca Ab | Aerosol formulations of peptides and proteins |
| US5955098A (en) * | 1996-04-12 | 1999-09-21 | Flemington Pharmaceutical Corp. | Buccal non polar spray or capsule |
| US7771746B2 (en) * | 1999-12-03 | 2010-08-10 | Polichem Sa | Methods for making sustained-release pharmaceutical compositions of ergot alkaloids having improved bioavailability and compositions thereof |
| ES2220724T3 (es) * | 2000-01-20 | 2004-12-16 | Basilea Pharmaceutica Ag | Composiciones de peptidos ciclicos administrables por via nasal. |
| US20030008005A1 (en) * | 2001-07-05 | 2003-01-09 | R.T. Alamo Ventures, Inc. | Sublingual administration of dihydroergotamine for the treatment of migraine |
| GB0208742D0 (en) | 2002-04-17 | 2002-05-29 | Bradford Particle Design Ltd | Particulate materials |
| GB2405334B (en) * | 2002-04-17 | 2006-02-15 | Nektar Therapeutics Uk Ltd | Particulate materials |
| KR20090129998A (ko) | 2007-02-11 | 2009-12-17 | 맵 파마슈티컬스, 인코포레이티드 | 부작용 프로파일을 최소화하면서 편두통의 빠른 완화를 가능하게 하는 ｄｈｅ의 치료적 투여 방법 |
| US20120000941A1 (en) * | 2010-06-30 | 2012-01-05 | Inspire Pharmaceuticals, Inc. | Medicine dispenser |
| EP3341059B1 (en) | 2015-09-10 | 2022-03-02 | Impel NeuroPharma Inc. | In-line nasal delivery device |
| CN110831578A (zh) * | 2017-07-02 | 2020-02-21 | 瑞迪博士实验室有限公司 | 双氢麦角胺的鼻用剂型 |
| EP3735244B1 (en) | 2018-01-05 | 2022-11-23 | Impel Pharmaceuticals Inc. | Intranasal delivery of dihydroergotamine by precision olfactory device |
| WO2020123607A1 (en) | 2018-12-11 | 2020-06-18 | Satsuma Pharmaceuticals, Inc. | Compositions, devices, and methods for treating or preventing headaches |
| GB2581431A (en) * | 2018-12-11 | 2020-08-19 | Satsuma Pharmaceuticals Inc | Compositions, devices, and methods for treating or preventing headaches |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1063512A (en) * | 1962-11-30 | 1967-03-30 | Benger Lab Ltd | Aerosols |
| GB1175430A (en) * | 1966-04-07 | 1969-12-23 | Sandoz Ltd | Pharmaceutical Compositions containing Ergot Alkaloids |
| CH507249A (de) * | 1968-05-31 | 1971-05-15 | Sandoz Ag | Verfahren zur Herstellung von 2-Brom-a-ergokryptin |
| CH534683A (de) * | 1970-05-26 | 1973-03-15 | Sandoz Ag | Verfahren zur Herstellung neuer Mutterkornpeptidalkaloide |
| CA990287A (en) * | 1972-09-26 | 1976-06-01 | Sandoz Patents Limited | 13-bromo-lysergic acid compounds |
| US4076715A (en) * | 1972-09-26 | 1978-02-28 | Sandoz Ltd. | 13-Bromo lysergic acid compounds |
| NL7314066A (cs) * | 1972-10-18 | 1974-04-22 | ||
| US3896228A (en) * | 1973-03-15 | 1975-07-22 | Sandoz Ltd | Method for treating nephrises |
| US3883655A (en) * | 1973-10-11 | 1975-05-13 | Sandoz Ltd | Ergocornine or 2-bromo-{60 -ergocyptine in the treatment of parkinsonism |
| DE2750090A1 (de) * | 1976-11-19 | 1978-06-01 | Sandoz Ag | Neue verabreichungsformen fuer organische verbindungen |
| EP0119493A1 (en) * | 1983-03-16 | 1984-09-26 | American Cyanamid Company | Use of copolymers of 2-acrylamido-2-methylpropane sulfonic acid for improving retention and dewatering in the manufacture of paper |
-
1977
- 1977-11-09 DE DE19772750090 patent/DE2750090A1/de not_active Ceased
- 1977-11-10 FI FI773376A patent/FI773376A7/fi not_active Application Discontinuation
- 1977-11-10 DK DK499477A patent/DK153440C/da not_active IP Right Cessation
- 1977-11-10 NO NO77773839A patent/NO773839L/no unknown
- 1977-11-10 SE SE7712693A patent/SE451944B/sv not_active IP Right Cessation
- 1977-11-15 NL NLAANVRAGE7712552,A patent/NL187892C/xx not_active IP Right Cessation
- 1977-11-15 GB GB47437/77A patent/GB1592563A/en not_active Expired
- 1977-11-15 CY CY1266A patent/CY1266A/xx unknown
- 1977-11-16 CA CA290,987A patent/CA1103585A/en not_active Expired
- 1977-11-16 GR GR54819A patent/GR65229B/el unknown
- 1977-11-17 NZ NZ185711A patent/NZ185711A/xx unknown
- 1977-11-17 HU HU77SA3075A patent/HU185924B/hu unknown
- 1977-11-17 IL IL7753419A patent/IL53419A/xx unknown
- 1977-11-17 PT PT67292A patent/PT67292B/pt unknown
- 1977-11-17 FR FR7734591A patent/FR2371454A1/fr active Granted
- 1977-11-17 IE IE2345/77A patent/IE46167B1/en not_active IP Right Cessation
- 1977-11-18 CS CS777615A patent/CS228502B2/cs unknown
- 1977-11-18 CS CS817502A patent/CS228523B2/cs unknown
- 1977-11-18 ES ES464275A patent/ES464275A1/es not_active Expired
- 1977-11-18 JP JP13803177A patent/JPS5366440A/ja active Granted
- 1977-11-18 AT AT0825477A patent/AT368881B/de active
- 1977-11-18 AU AU30783/77A patent/AU520754B2/en not_active Expired
-
1978
- 1978-01-19 DE DE19782802113 patent/DE2802113A1/de not_active Withdrawn
-
1980
- 1980-08-15 PH PH24447A patent/PH23643A/en unknown
-
1981
- 1981-12-08 US US06/328,680 patent/US4462983A/en not_active Expired - Lifetime
-
1984
- 1984-09-01 SG SG617/84A patent/SG61784G/en unknown
- 1984-09-13 KE KE3453A patent/KE3453A/xx unknown
- 1984-11-08 HK HK859/84A patent/HK85984A/xx not_active IP Right Cessation
- 1984-12-30 MY MY55/84A patent/MY8400055A/xx unknown
-
1986
- 1986-06-09 US US06/871,985 patent/US4758423A/en not_active Expired - Lifetime
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