WO1989004828A1 - Cyclodextrin clathrates of 5-cyano-prostacycline derivatives and their use as drugs - Google Patents

Cyclodextrin clathrates of 5-cyano-prostacycline derivatives and their use as drugs

Info

Publication number
WO1989004828A1
WO1989004828A1 PCT/DE1988/000739 DE8800739W WO8904828A1 WO 1989004828 A1 WO1989004828 A1 WO 1989004828A1 DE 8800739 W DE8800739 W DE 8800739W WO 8904828 A1 WO8904828 A1 WO 8904828A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
acid
free
chain
cyano
Prior art date
Application number
PCT/DE1988/000739
Other languages
German (de)
English (en)
French (fr)
Inventor
Werner Skuballa
Helmut Dahl
Helmut VORBRÜGGEN
Olaf Loge
Karl-Heinz Thierauch
Original Assignee
Schering Aktiengesellschaft
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Schering Aktiengesellschaft filed Critical Schering Aktiengesellschaft
Publication of WO1989004828A1 publication Critical patent/WO1989004828A1/de
Priority to GB8916355A priority Critical patent/GB2231045B/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
    • C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
    • C07D307/937—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins
    • 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
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
    • C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes

Definitions

  • the present invention relates to cyclodextrin clathrates of 5-cyano-prostacyclin analogs and agents containing them.
  • 5-cyano-prostacyclin analogs are pharmacologically and medically valuable active substances, the production and use of which are described, for example, in DE-OS 2753244. These substances have a significantly improved specificity and, above all, a much longer effect compared to natural prostacyclin with a similar spectrum of activity.
  • inclusion compounds of these 5-cyano-prostacyclin analogs with cyclodextrins do not have the disadvantages mentioned, i.e. their water solubility is improved, the rate of dissolution is increased, and the inclusion compounds are in crystalline form. In addition, their stability to heat, light and oxygen is increased and their galenical preparation (preparation of solutions or tablets) is facilitated.
  • the invention relates to cyclodextrin clathrates of 5-cyano-prostacyclin analogs of the general formula I.
  • R 5 wo ⁇ the radical OR_, where R. can be hydrogen, alkyl, cycloalkyl, aryl or a heterocyclic radical, or the radical NHR, with R, in the
  • B is a straight-chain or branched-chain alkyl group with 2-10 C atoms
  • W is a free or functionally modified hydroxymethylene group
  • OH group can be ⁇ or ⁇
  • D is a straight-chain or branched alkylene group with 1-5 C atoms
  • E is an oxygen or sulfur atom or a direct bond.
  • R is an alkyl, cycloalkyl, or an optionally substituted aryl or a heterocyclic group
  • R- a free or functionally modified hydroxy group and, if R represents hydrogen, the salts thereof with physiologically compatible bases.
  • alkyl group R straight or branched alkyl groups with 1-10 C atoms are to be considered, such as methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl. Heptyl, hexyl, decyl.
  • the alkyl groups R can optionally be substituted 1 to more times by halogen atoms, alkoxy groups, optionally substituted aryl groups, dialkylamines and trialkyla monium.
  • Preferred alkyl groups are those which are monosubstituted. Examples of substituents are fluorine, chlorine or bromine atoms, phenyl, dimethylamino, diethylamino, methoxy, ethoxy.
  • alkyl groups R are those with 1-4 carbon atoms, such as. For example, methyl, ethyl, propyl, dimethylaminopropyl, isobutyl, butyl.
  • Suitable aryl groups R are both substituted and unsubstituted aryl groups, such as, for example, phenyl, 1-naphthyl and 2-naphthyl, which can each be substituted by 1-3 halogen atoms, one phenyl group, 1-3 alkyl groups each with 1-4 C atoms, a chloromethyl, fluoromethyl, trifluoromethyl, carboxyl, hydroxyl or alkoxy group with 1-4 C atoms.
  • the substituents in the 3- and 4-position on the phenyl ring are preferred, for example by fluorine, chlorine, alkoxy or trifluoromethyl or in 4-position by hydroxy.
  • the cycloalkyl group R can contain 4-10, preferably 5 and 6 carbon atoms in the ring.
  • the rings can be substituted by alkyl groups with 1-4 carbon atoms. Examples include cyclopentyl, cyclohexyl, methylcyclohexyl and adamantyl.
  • Suitable heterocyclic groups are 5- and 6-membered heterocycles which contain at least 1 heteroatom, preferably nitrogen, oxygen or sulfur. Examples include 2-furyl, 2-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl and others.
  • acids are organic carboxylic acids and sulforic acid with 1-15 carbon atoms, which belong to the aliphatic, cyclo-aliphatic, aromatic, aromatic-aliphatic and heterocyclic series. These acids can be saturated, unsaturated and / or polybasic and / or substituted in the usual way.
  • substituents are alkyl, hydroxy, alkoxy, oxo or amino groups or halogen atoms.
  • Examples include the following carboxylic acids: formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, Caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecyl acid, Saurincherre, tridecylic acid, myristic acid, pentadecylic acid, trimethyl- acetic acid, cyclopentylacetic acid, cyclohexylacetic acid, Cyclopropancarbonkla- acid, cyclohexanecarboxylic acid, phenylacetic acid, phenoxyacetic acid, methoxyacetic acid, ⁇ thoxyessigkla, mono-, di- - and trichloroacetic acid, aminoacetic acid, diethyla inoacetic acid, piperidinoacetic acid, morpholinoacetic acid, lactic acid, succinic acid, adipic acid, benzoic acid, be
  • sulfonic acids include methanesulfonic acid, ethanesulfonic acid, isopropanesulfonic acid, ⁇ -chloroethanesulfonic acid, butanesulfonic acid, cyclopentanesulfonic acid, cyclohexanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, p-chlorobenzenesulfonic acid, NN-dimethylaminosulfonic acid, N, N-diethylaminosulfonic acid - (ß-Chloroethyl) aminosulfonic acid, pyrrolidino, piperidino, piperazino, N-methylpiperazino and morpholinosulfonic acid in question.
  • hydroxyl groups R_ and in W can be functionally modified, for example
  • ether and acyl radicals are suitable as ether and acyl radicals. Easily removable ether residues such as, for example, the tetrahydropyranyl, tetrahydrofuranyl, ⁇ -ethoxyethyl, trimethylsilyl, dimethyl-tert-butyl-silyl and tri-p-benzyl-silyl radical are preferred.
  • acyl radicals as those mentioned for R come into question; Examples include acetyl, propionyl, butyryl, and Bezzoyl.
  • Suitable alkyl groups R are straight-chain and branched-chain, saturated and unsaturated alkyl radicals, preferably saturated, with 1-10, in particular 1-6, carbon atoms, which may be substituted by optionally substituted aryl. Examples include methyl, ethyl, pro-, pyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, butenyl, isobutenyl, propenyl, Pentenyl, benzyl and p-chlorobenzyl.
  • the cycloalkyl group can contain 4-10, preferably 5 and 6 carbon atoms in the ring.
  • the rings can be substituted by alkyl groups with 1-4 carbon atoms. Examples include cyclopentyl, cyclohexyl, methylcyclohexyl and adamantyl.
  • Suitable substituted or unsubstituted aryl groups R are: phenyl, 1-naphthyl and 2-naphthyl, which can each be substituted by 1-3 halogen atoms, one phenyl group, 1-3 alkyl groups each having 1-4 C atoms, one Chloromethyl, fluoromethyl, trifluoromethyl, carboxy, alkoxy or hydroxy group.
  • the substitution in the 3- and 4-position on the phenyl ring is preferred, for example by fluorine, chlorine, alkoxy or trifluoromethyl or in the 4-position by hydroxy.
  • Suitable heterocyclic groups R are 5- and 6-membered heterocycles which contain at least 1 heteroatom, preferably nitrogen, oxygen or sulfur. Examples include 2-furyl, 2-thienyl, 2-pyridyl, 3-pyridyl-, 4-pyridyl and others.
  • Suitable alkylene groups B are straight-chain or branched-chain, saturated and unsaturated alkylene radicals, preferably saturated with 2-10, in particular 2-5, carbon atoms. Examples include ethylene, 1,2-propylene, ethyl ethylene, trimethylene, tetramethylene, pentamethylene and others.
  • Suitable alkylene groups D are straight-chain saturated 1-5 or branched-chain saturated alkylene radicals having 2-5 carbon atoms.
  • the radicals mentioned for B come into consideration as examples.
  • the compounds of general formula I are dissolved in a pharmaceutically acceptable solvent, for example an alcohol, preferably ethanol, a ketone, for example acetone or an ether, for example diethyl ether, and with aqueous solutions of ⁇ -, ⁇ - or f-Cyclodextrin, preferably ⁇ -cyclodextrin, mixed at 20-80 ° C, or the acids in the form of the aqueous solutions of their salts, for example the sodium or potassium salts, are mixed with the cyclodextrin and after solution with the equivalent amount of a Acid, for example hydrochloric acid or sulfuric acid.
  • a pharmaceutically acceptable solvent for example an alcohol, preferably ethanol, a ketone, for example acetone or an ether, for example diethyl ether
  • the clathrates can be obtained in a stoichiometric composition with a reproducible active ingredient content.
  • the clathrates made in accordance with this invention are valuable pharmaceuticals.
  • the clathrates can be used in their anhydrous, hygroscopic form or in an aqueous, less hygroscopic form.
  • the new clathrates of 5-cyano-prostacyclins according to Formula I are in the stoichiometric ratio of carbacyclin: cyclodextrin or have a higher cyclodextrin content.
  • 5-cyano-16-methyl-prostacyclin forms a complex of the composition 1: 2.5 (12.12 l of prostacyclin) or any lower values with ⁇ -cyclodextrin.
  • the clathrates made in accordance with this invention are valuable pharmaceuticals.
  • the clathrates of this invention are hypotensive and bronchodilatory. They are also suitable for inhibiting platelet aggregation. They have a cytoprotective effect on the stomach, intestine, heart, liver, kidney and pancreas. Consequently, the new cyclodextrin clathrates of the formula I are valuable pharmaceutical active substances. In addition, with a similar spectrum of activity, they have a higher specificity and, above all, a substantially longer activity compared to corresponding prostaglandins. Compared to PGI, they are characterized by greater stability.
  • the high tissue specificity of the new prostaglandia is shown in the examination on smooth-muscular organs, such as on the guinea pig ileum or on the isolated rabbit trachea, where a considerably lower stimulation can be observed than when applying natural prostaglandi from E, A or F -Type.
  • the new 5-cyano-prostacyclin clathrates have the properties typical of prostacyclins, such as, for example, lowering the peripheral arterial and coronary vascular resistance, inhibiting platelet aggregation and dissolving platelet thrombi, myocardial cytoprotection and thus lowering the systemic blood pressure and without simultaneously reducing stroke volume reduce coronary blood flow; Treatment of stroke, prophylaxis and therapy of coronary heart disease, coronary thrombosis, myocardial infarction, peripheral artery disease, arteriosclerosis and thrombosis, prophylaxis and therapy of ischemic attacks of the CNS system, therapy of shock, inhibition of bronchoconstriction, inhibition of the bronchoconstriction Gastric acid secretion, cytoprotection of the gastric and intestinal mucosa, cytoprotection in the liver, kidney, heart and pancreas, also in organ transplants, anti-allergic properties, reduction in pulmonary vascular resistance and pulmonary blood pressure, promotion of renal blood flow,
  • carbacyclins of this invention can also be used in combination, for example with ⁇ -blockers or diuretics.
  • the 5-cyano-prostacyclin clathrates of this invention can also be used in combination, for example with ⁇ -blockers, diuretics, phosphonic diester inhibitors, calcium antagonists, non-steroidal anti-inflammatories, leukotriene synthesis inhibitors, leukotriene antagonists, thromboxane synthesis inhibitors or thromboxane antagonists.
  • the clathrates according to the invention can be used in liquid or solid pharmaceutical formulations, the formulations being able to be administered enterally, parenterally, vaginally or rectally, or they can also be incorporated into surgical sutures and plastics.
  • the prostaglandin-cyclodextrin clathrate with carrier substances and auxiliary substances such as lactoxes is used to manufacture tablets.
  • aqueous cyclodextrin clathrate solutions are lyophilized together with lactose.
  • the lyophilisates can then be brought to the desired concentration with physiological saline.
  • the invention therefore includes pharmaceutical preparations and formulations which contain a cyclodextrin clathrate of a carbacyclin analog as the active ingredient.
  • the content of prostacyclinanol in the clathrate was determined by post-pressure liquid chromatography and was 4%.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Nanotechnology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Medical Informatics (AREA)
  • Materials Engineering (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Furan Compounds (AREA)
PCT/DE1988/000739 1987-11-27 1988-11-25 Cyclodextrin clathrates of 5-cyano-prostacycline derivatives and their use as drugs WO1989004828A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB8916355A GB2231045B (en) 1987-11-27 1989-07-18 Cyclodextrin clathrates of 5-cyano-16 -methylprostacyclin and their use in pharmacetical compositions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP3740838.0 1987-11-27
DE19873740838 DE3740838A1 (de) 1987-11-27 1987-11-27 Cyclodextrinclathrate von 5-cyano-prostacyclinderivaten und ihre verwendung als arzneimittel

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Publication Number Publication Date
WO1989004828A1 true WO1989004828A1 (en) 1989-06-01

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PCT/DE1988/000739 WO1989004828A1 (en) 1987-11-27 1988-11-25 Cyclodextrin clathrates of 5-cyano-prostacycline derivatives and their use as drugs

Country Status (11)

Country Link
US (1) US5010065A (en, 2012)
EP (1) EP0349621A1 (en, 2012)
JP (1) JPH02502379A (en, 2012)
AT (1) AT396687B (en, 2012)
BE (1) BE1001327A3 (en, 2012)
CH (1) CH677790A5 (en, 2012)
DE (1) DE3740838A1 (en, 2012)
FR (1) FR2623807B1 (en, 2012)
GB (1) GB2231045B (en, 2012)
IT (1) IT1227576B (en, 2012)
WO (1) WO1989004828A1 (en, 2012)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993007875A1 (de) * 1991-10-22 1993-04-29 Schering Aktiengesellschaft Verwendung von prostacyclin-derivaten zur verhinderung oder behandlung von störungen der mikrozirkulation bei gabe von röntgen-, nmr- oder ultraschallkontrastmitteln
WO2008009426A1 (en) * 2006-07-18 2008-01-24 Bayer Schering Pharma Aktiengesellschaft 5-cyano-prostacyclin derivatives as agents for the treatment of autoimmune diseases

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Publication number Priority date Publication date Assignee Title
US5227372A (en) * 1990-03-07 1993-07-13 Children's Medical Center Corporation Method for retaining ophthalmological agents in ocular tissues
DE4104607A1 (de) * 1991-02-12 1992-08-13 Schering Ag Prostacyclin- und carbacyclinderivate als mittel zur behandlung von fiebrigen erkrankungen
US5694021A (en) * 1994-02-28 1997-12-02 Kabushiki Kaisha Toshiba System for executing charge control of a secondary battery and detecting the capacitance thereof
US5896596A (en) * 1997-10-22 1999-04-27 Nitto Kogyo Co., Ltd. Apparatus for generating massaging water stream
JP5271272B2 (ja) 2006-11-16 2013-08-21 ジェンムス ファーマ インコーポレイティド Ａ型インフルエンザウィルス感染の治療のための薬剤としてのｅｐ２およびｅｐ４作動薬
JP2013508282A (ja) 2009-10-14 2013-03-07 ジェンムス ファーマ インコーポレイティド ウイルス感染のための併用療法処置
US20160184387A1 (en) 2013-08-09 2016-06-30 Dominique Charmot Compounds and methods for inhibiting phosphate transport
WO2020237096A1 (en) 2019-05-21 2020-11-26 Ardelyx, Inc. Combination for lowering serum phosphate in a patient

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Publication number Priority date Publication date Assignee Title
DE2840142A1 (de) * 1977-09-23 1979-04-05 Chinoin Gyogyszer Es Vegyeszet Die mit cyclodextrin gebildeten einschlusskomplexe des prostacyclins und seiner derivate sowie verfahren zur herstellung dieser komplexe
DE2753244A1 (de) * 1977-11-25 1979-06-07 Schering Ag Neue prostacyclinderivate und verfahren zu ihrer herstellung
DE3427797A1 (de) * 1984-07-25 1986-02-06 Schering AG, 1000 Berlin und 4709 Bergkamen Zytoprotektive wirkung von prostacyclin-derivaten an leber, bauchspeicheldruese und niere

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JPS503362B1 (en, 2012) * 1970-06-10 1975-02-04
DE2405146A1 (de) * 1974-01-31 1975-08-07 Siemens Ag Mengenmessgeraet mit einem in einer kammer angeordneten rotor
DE2912409A1 (de) * 1978-03-31 1979-10-11 Ono Pharmaceutical Co 6,9-methano-pgi tief 2 -analoge
JPS5540923A (en) * 1978-09-14 1980-03-22 Ono Sokki Co Ltd Flow meter
JPS56150039A (en) * 1980-04-22 1981-11-20 Sankyo Co Ltd Clathrate compound of prostacycline derivative
DE3608088C2 (de) * 1986-03-07 1995-11-16 Schering Ag Pharmazeutische Präparate, enthaltend Cyclodextrinclathrate von Carbacyclinderivaten

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Publication number Priority date Publication date Assignee Title
DE2840142A1 (de) * 1977-09-23 1979-04-05 Chinoin Gyogyszer Es Vegyeszet Die mit cyclodextrin gebildeten einschlusskomplexe des prostacyclins und seiner derivate sowie verfahren zur herstellung dieser komplexe
DE2753244A1 (de) * 1977-11-25 1979-06-07 Schering Ag Neue prostacyclinderivate und verfahren zu ihrer herstellung
DE3427797A1 (de) * 1984-07-25 1986-02-06 Schering AG, 1000 Berlin und 4709 Bergkamen Zytoprotektive wirkung von prostacyclin-derivaten an leber, bauchspeicheldruese und niere

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Title
Chem. Pharm. Bull., Band. 29, Nr. 1, 1981, Kaneto Uekama et al.: "Effects of Cyclodextrins on the Hydrolysis of Prostacyclin and its Methyl Ester in Aqueous Solution", Seite 213-219. *
Chemical Abstracts, Band 103, Nr. 6, 12 August 1985, (Columbus, Ohio, US), Stadler-Szoke, Agnes et al.: "Examples of the application of cyclodextrin in formulation of oral drug preparations", Seite 342, Zusammenfassung 42472f, & J. Inclusion Phenom. 1984, 2(3-4) 503-1. *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993007875A1 (de) * 1991-10-22 1993-04-29 Schering Aktiengesellschaft Verwendung von prostacyclin-derivaten zur verhinderung oder behandlung von störungen der mikrozirkulation bei gabe von röntgen-, nmr- oder ultraschallkontrastmitteln
US5814301A (en) * 1991-10-22 1998-09-29 Schering Aktiengesellschaft Use of prostacyclin derivatives to prevent or to treat disorders of the microcirculatory system when x-ray, NMR or ultrasonic contrast media are administered
WO2008009426A1 (en) * 2006-07-18 2008-01-24 Bayer Schering Pharma Aktiengesellschaft 5-cyano-prostacyclin derivatives as agents for the treatment of autoimmune diseases

Also Published As

Publication number Publication date
FR2623807B1 (fr) 1990-08-31
JPH02502379A (ja) 1990-08-02
FR2623807A1 (fr) 1989-06-02
US5010065A (en) 1991-04-23
EP0349621A1 (de) 1990-01-10
IT1227576B (it) 1991-04-16
GB2231045B (en) 1992-04-29
AT396687B (de) 1993-11-25
GB2231045A (en) 1990-11-07
IT8822760A0 (it) 1988-11-28
DE3740838A1 (de) 1989-06-08
CH677790A5 (en, 2012) 1991-06-28
ATA901688A (de) 1993-03-15
BE1001327A3 (fr) 1989-09-26
GB8916355D0 (en) 1990-07-04

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