EP0918544A2 - Polymere gallensäure-resorptionsinhibitoren mit gleichzeitiger gallensäure-adsorberwirkung - Google Patents
Polymere gallensäure-resorptionsinhibitoren mit gleichzeitiger gallensäure-adsorberwirkungInfo
- Publication number
- EP0918544A2 EP0918544A2 EP97940028A EP97940028A EP0918544A2 EP 0918544 A2 EP0918544 A2 EP 0918544A2 EP 97940028 A EP97940028 A EP 97940028A EP 97940028 A EP97940028 A EP 97940028A EP 0918544 A2 EP0918544 A2 EP 0918544A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkylene
- alkyl
- compounds according
- nhr
- phenylene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F246/00—Copolymers in which the nature of only the monomers in minority is defined
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
Definitions
- the invention relates to polymers with bile acid absorption inhibitor and simultaneous bile acid adsorber effect, a process for their preparation and the use of these polymers as medicaments.
- Bile acids and their salts are natural detergents and have an important physiological function in fat digestion and fat absorption. As end products of the choiesterin metabolism, they are synthesized in the liver, stored in the gallbladder and released from there as part of the bile into the intestine, where they exert their physiological effect. The major part (approx. 85-90%) of the secreted bile acids (approx. 16 g / day) is resorbed from the intestinal wall via the enterohepatic circulation, preferably in the terminal lieum, and transported back to the liver, ie recycled. Only 10-15% of the bile acids are excreted in the faeces.
- a reduction in the amount of bile acid by post-synthesis of bile acids from cholesterol can be compensated to a certain extent via a control loop system.
- a decrease in the liver cholesterol level leads to an increase in the absorption of cholesterol from the blood serum and thus lowers the cholesterol level in the blood serum.
- the enterohepatic circulation can be interrupted and the serum cholesterol level in the blood can be reduced by suppressing the bile acid reabsorption by means of suitable inhibitors or bile acid adsorbers in the intestine. Too high a serum cholesterol level is considered to be of concern in medicine because it leads to atherosclerosis and thus the risk of heart attack increases. Therefore, there are many therapeutic approaches for the treatment of hypercholesterolemia.
- One of these approaches is to interrupt the enterohepatic cycle. With this approach, all diseases can also are treated in which an inhibition of bile acid reabsorption in the small intestine appears desirable.
- Non-absorbable polymers have been used therapeutically for some time to bind bile acids.
- insoluble, mostly crosslinked polymers are used for this purpose, which contain quaternized nitrogen centers and act in a similar way to anion exchangers.
- These polymers bind part of the bile acid anions present in the intestine via predominantly ionic interactions and transport them out of the intestine.
- Commercial products of this type contain e.g. the active substances cholestyramine and colestipol. For example, they are used to treat hypercholesterolemia.
- Bile acid absorption inhibitors (receptor blockers):
- Bile acid receptor sites in the terminal ileum are blocked by molecules which, like the bile acids, can interact with the receptors but, unlike the bile acids, are not absorbed. Due to this receptor blockade, the bile acids can no longer be absorbed and are then excreted with the faeces. Examples of polymeric bile acid receptor blockers can be found in EP 0 549 967. This describes bile acid polymers and oligomers in which bile acid molecules are laterally linked to a polymer backbone.
- the previously known adsorbers are not selective enough and also bind vitamins (eg vitamin K) and other physiologically important substances, so that deficiency symptoms (eg avitaminoses) can occur.
- bile acid molecules or low-molecular bile acid absorption inhibitor molecules are bound covalently or via a spacer group to a polymer molecule, so that they are no longer self-absorbable but still retain their absorption-inhibiting effect.
- the polymer is too large to be absorbed.
- the polymer also contains bile acid adsorbent centers, e.g. B. quaternized nitrogen centers in the molecule.
- Polymers of this type therefore have a dual effect. On the one hand, they act as polymeric bile acid absorption inhibitors due to the covalently firmly bound receptor blocker units and, on the other hand, as bile acid adsorbers.
- the invention therefore relates to vinyl copolymers consisting of units of the formula
- R 1 , R 2 , R 3 are hydrogen or CH 3 ;
- R 4 , R 5 are hydrogen, (C r C 6 ) alkyl, (C r C 6 ) acyl; d 0.01 to 1.00; e 0 to 0.99; f 0 to 0.99; where d + e + f must be 1;
- H is a bond, -CH 2 -, -Ar-, -Ar-CH 2 -, where Ar is phenylene, naphthylene m 1 to 18; n 1 to 18;
- R 7 -OH, -O- (C r C e ) alkyl, -NH 2 ;
- crosslinker selected from the group consisting of:
- R 1 , R 2 , R 3 are hydrogen or CH 3 ;
- R 4 , R 5 are hydrogen; d 0.01 to 1.00; e 0 to 0.99; f 0 to 0.99; where d + e + f must be 1;
- H is a bond, -CH 2 -;
- R 1 , R 2 , R 3 are hydrogen; R 4 , R 5 are hydrogen; d 0.01 to 1.00; e 0 to 0.99; f 0 to 0.99; where d + e + f must be 1;
- H is a bond, -CH 2 -;
- Physiologically compatible acid addition salts are understood as meaning compounds which are readily soluble, soluble and slightly soluble in water as defined in the "German Pharmacopoeia” (9th edition 1986, official edition, German Pharmacist Publishing House Stuttgart), page 19.
- the hydrochlorides and sulfates of the compounds are preferred.
- ammonium center is understood to mean a positively charged nitrogen atom (quaternized).
- the invention further relates to a process for the preparation of the polymers consisting of units of the formula I.
- the cholate-containing monomers were synthesized as described in the examples.
- Attachment of a linker to cholic acid and subsequent polymer-analogous reaction with a polymer containing cholic acid is first mesylated with methanesulfonyl chloride in a basic medium.
- the Mesyl group is a good leaving group and enables the attachment of side chains, eg a triethylene glycol unit, through nucleophilic substitution.
- the free hydroxyl group of the triethylene glycol unit is then selectively activated by reaction with tosyl chloride.
- the tosyl leaving group formed in this way enables polymer-analogous reaction with polymers containing amino groups, for example polyallylamine or polyvinylamine. (Example 1d).
- the degree of substitution can be adjusted by changing the ratio of polyamine: cholic acid derivative.
- Cholic acid is first converted into the active ester with p-nitrophenol.
- the amido ether is then obtained by reaction with 2-methoxyethylamine (Example 3b). This is linked to an amino group-containing polymer as described in Method 1 via a linker.
- An acrylic-substituted cholic acid derivative is reacted by radical copolymerization with a vinyl (preferably acrylic) monomer (see Example 5). Any ester groups still present in the cholate residue can be selectively saponified under basic conditions.
- Allylamine (hydrochloride) and other radically polymerizable vinyl amines can be polymerized directly with acrylic-substituted cholic acid derivatives (Examples 11, 16).
- an acrylic-substituted cholic acid derivative in alcoholic solution at pH 9-10 in a Michael addition with an amino group-containing polymer, e.g. a polyamine.
- the present invention also relates to pharmaceutical preparations which contain one or more of the active compounds according to the invention and optionally further lipid-lowering agents.
- the active compounds according to the invention are suitable for use as lipid-lowering drugs.
- the active compounds according to the invention are used, for example, as pharmaceutical preparations, food additives, formulation auxiliaries, detergents, medications for influencing the enterohepatic circulation of bile acids, medications for influencing lipid absorption, medications for influencing serum cholesterol levels, medications for concentration-dependent inhibition of bile acid absorption in the gastrointestinal medication used to prevent arteriosclerotic symptoms.
- Adduct of triethylene glycol with cholic acid Adduct of triethylene glycol with cholic acid:
- Example 1a 6.1 g (12.5 mmol) of Example 1a were suspended in 25 ml (150 mmol) of triethylene glycol and dissolved by briefly heating to 100 ° C. 4.0 g (100 mmol) of magnesium oxide were added and the mixture was stirred at 100 ° C. for 5 h. After standing overnight, 100 ml of methylene chloride were added and the precipitate formed was suction filtered and washed with methylene chloride. The organic phase was washed with 200 ml of 2N aq. Hydrochloric acid extracted and then concentrated. Crude yield: 7.2 g.
- Example 3b 4.1 g (9.9 mmol) of Example 3b were dissolved in 20 ml of pyridine. At 0 ° C 0.92 ml methanesulfonyl chloride was added and the mixture for 30 min at 0 ° C and 1 h at room temperature. touched. Ice was added to the mixture. Then 20 ml of conc. Sulfuric acid stirred in. The mixture was stirred for a further 5 minutes. The resulting precipitate was filtered off, washed with water and then taken up in dichloromethane. This solution was extracted with water. The organic phase was evaporated after drying over sodium sulfate. Crude yield: 4.7 g. The crude product was purified by column chromatography on silica gel (ethyl acetate). Yield: 2.9g (54%) Example 3c.
- Example 9a To a solution of 55 mg (77 ⁇ mol) Example 9a and 17 mg (77 ⁇ mol) trimethylammonium propyl methacrylate chloride in 3 ml water were added 0.52 mg free radical initiator VA 044 (from Wako). The mixture was degassed and then stirred at 45 ° C for 70 h. The mixture was evaporated and the residue was dissolved in 10 ml of water and purified by ultrafiltration (membrane 5000 ⁇ ). After freeze-drying, 66 mg of Example 9b were obtained.
- Example 9a Nitrogen was bubbled through a solution of 741 mg (1.0 mmol) of Example 9a in 3.5 ml of methanol for 30 minutes. The solution was then heated to 60 ° C. 10 mg of VA 044 radical initiator (from Wako) were added. The mixture was then stirred at 60 ° C. for 4 hours under a nitrogen atmosphere. It was then diluted with water and purified by ultrafiltration (membrane 5000 A). To exchange the counterion Br “ - Cl " , it was then washed twice with dilute aqueous NaCl solution and then twice with water. After freeze-drying, 456 mg were obtained.
- VA 044 radical initiator from Wako
- the product was isolated by ultrafiltration in water (membrane 5000A) and subsequent freeze-drying. Yield: 90 mg.
- the bovine bile assay adsorption test measures the polymer's ability to adsorb bile acids.
- the samples were prepared as follows:
- aqueous solution which contains the following salts in the concentrations given below:
- HPLC system from Kontron, consisting of three pumps and
- Enzyme solution 3-alpha-hydroxysteroid dehydrogenase 0.5 units / ml
- the batches are mixed and incubated for 2 hours at room temperature.
- HPLC system from Kontron, consisting of three pumps and mixing chamber, autosampler, UV detector and evaluation unit with software MT2.
- Mobile phase mobile phase A: ammonium carbamate buffer 0.019 M, with
- TDC Taurodeoxycholate
- GDC Glycodesoxycholate
- TCDC Taurochenodeoxycholate
- Rat intestine perfused in vivo examines the ability of the polymers to block bile acid reabsorption in the area of the ileum.
- Rat intestine perfused in vivo The in vivo investigation was carried out as in FGJ Poelma et al. (J. Pharm. Sci. 78 (4), 285-89, 1989) - modifications of the test are given.
- taurocholate and taurocholic acid or cholate and cholic acid are used synonymously.
- the bile duct is dissected and a catheter is integrated (PE 50, Intramedic®).
- PE 50 Intramedic®
- an adapter for holding 100 ⁇ l disposable pipette tips was attached.
- the bile is collected in these pipettes and filled into balanced Eppendorf reaction vessels at certain intervals.
- the bile, as well as the medium samples are weighed out and aliquots are measured in the scintillation counter.
- 10 ⁇ l sample are pipetted into a Sarstedt sample vessel, 58 x 22 mm, mixed with 10 ml Quickszint 212 (Zinsser GmbH, Frankfurt am Main, Germany) and counted in a Beckman 2800 ß counter after 30 min.
- Wistar rats from our own breeding with an average body weight of 230-290 g are used as test animals.
- the test animals are not starved before anesthesia (urethane 1 g / kg ip).
- the animals are anesthetized on a temperature-controlled (constant 37 ° C) operating table (Medax), sheared on the abdominal side and then the abdominal wall is opened to the animals with an approx. 7 cm long incision.
- a Luer adapter Feinmechanik Hoechst
- the small intestine is tied in and tied further 13-14 cm to the beginning of the small intestine.
- the contents of this intestinal segment are carefully rinsed out with 37 ° C warm isotonic saline.
- the test solution is later instilled in this segment, the end of the jejunum beginning of the ileum.
- the pump tubing is connected to the intestinal segment with two Luer adapters and the residual solution is filled in via a three-way valve (Pharmascal K 75a) and a 2 ml disposable syringe (Chirana) the medium is pumped at 0.25 ml / min
- a three-way valve Pharmascal K 75a
- a 2 ml disposable syringe Chirana
- the medium is pumped at 0.25 ml / min
- the bovine bile assay adsorption test shows that the polymers according to the invention have a significantly greater ability to adsorb bile acids than the substance of Example 15 from EP 0 549 967.
- the polymers according to the invention have a similarly high ability to adsorb bile acids as cholestyramine.
- the polymers according to the invention show an absorption-inhibiting effect of 36% to 60%.
- cholestyramine shows a smaller absorption-inhibiting effect of 25%.
- the polymers according to the invention are thus also superior in their action to cholestyramine since, in addition to their great ability to adsorb bile acids, they are themselves well bound to the bile acid receptor and thus show a resorption-inhibiting effect.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Polymers & Plastics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19633268 | 1996-08-19 | ||
DE19633268A DE19633268A1 (de) | 1996-08-19 | 1996-08-19 | Polymere Gallensäure-Resorptionsinhibitoren mit gleichzeitiger Gallensäure-Adsorberwirkung |
PCT/EP1997/004049 WO1998007449A2 (de) | 1996-08-19 | 1997-07-25 | Polymere gallensäure-resorptionsinhibitoren mit gleichzeitiger gallensäure-adsorberwirkung |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0918544A2 true EP0918544A2 (de) | 1999-06-02 |
Family
ID=7802940
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP97940028A Withdrawn EP0918544A2 (de) | 1996-08-19 | 1997-07-25 | Polymere gallensäure-resorptionsinhibitoren mit gleichzeitiger gallensäure-adsorberwirkung |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0918544A2 (de) |
JP (1) | JP2000517356A (de) |
CA (1) | CA2263671A1 (de) |
DE (1) | DE19633268A1 (de) |
WO (1) | WO1998007449A2 (de) |
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JP3942846B2 (ja) * | 2001-06-21 | 2007-07-11 | 独立行政法人科学技術振興機構 | 組織特異的トランスポーター阻害剤 |
EP1555327A4 (de) * | 2002-10-16 | 2006-08-02 | Kyowa Medex Co Ltd | Verfahren und reagenz zur messung von cholesterin in lipoproteinen hoher dichte |
HUE030062T2 (en) | 2010-11-08 | 2017-04-28 | Albireo Ab | IBAT inhibitors for the treatment of liver diseases |
PT2637646T (pt) | 2010-11-08 | 2016-08-17 | Albireo Ab | Uma combinação farmacêutica que compreende um inibidor do ibat e um sequestrador de ácido biliar |
JO3301B1 (ar) | 2013-04-26 | 2018-09-16 | Albireo Ab | تعديلات بلورية على إيلوبيكسيبات |
CN105377994B (zh) | 2013-08-22 | 2018-03-02 | 索尼公司 | 水溶性荧光染料或有色染料及其使用方法 |
KR20220082931A (ko) | 2014-06-25 | 2022-06-17 | 이에이 파마 가부시키가이샤 | 고형 제제 및 그의 착색 방지 또는 착색 감소 방법 |
EP3012252A1 (de) | 2014-10-24 | 2016-04-27 | Ferring BV | Kristalline Form von elobixibat |
KR20170120677A (ko) | 2015-02-26 | 2017-10-31 | 소니 주식회사 | 접합 그룹을 포함하는 수용성 형광 또는 착색 염료 |
CA3011565C (en) | 2016-02-09 | 2024-01-02 | Albireo Ab | Oral cholestyramine formulation and use thereof |
US10441605B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Oral cholestyramine formulation and use thereof |
US10786529B2 (en) | 2016-02-09 | 2020-09-29 | Albireo Ab | Oral cholestyramine formulation and use thereof |
RU2750937C2 (ru) | 2016-02-09 | 2021-07-06 | Альбирео Аб | Пероральный состав холестирамина и его применение |
US10441604B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Cholestyramine pellets and methods for preparation thereof |
CA3231845A1 (en) | 2016-04-01 | 2017-10-05 | Sony Group Corporation | Ultra bright dimeric or polymeric fluorescent and colored dyes |
BR112018073199A2 (pt) | 2016-05-11 | 2019-04-16 | Sony Corporation | corantes diméricos ou poliméricos ultrabrilhantes |
CA3071285A1 (en) | 2017-08-09 | 2019-02-14 | Albireo Ab | Cholestyramine granules, oral cholestyramine formulations and use thereof |
WO2019032027A1 (en) | 2017-08-09 | 2019-02-14 | Albireo Ab | CHOLESTYRAMINE TABLETS, ORAL FORMULATIONS OF CHOLESTYRAMINE AND THEIR USE |
WO2019099789A1 (en) | 2017-11-16 | 2019-05-23 | Sony Corporation | Programmable polymeric drugs |
US20210128591A1 (en) * | 2017-12-13 | 2021-05-06 | Sony Corporation | Ionic polymers comprising biologically active compounds |
EP3769085B1 (de) | 2018-03-19 | 2022-08-24 | Sony Group Corporation | Verwendung von zweiwertigen metallen zur verstärkung von fluoreszenzsignalen |
US10793534B2 (en) | 2018-06-05 | 2020-10-06 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
WO2019234077A1 (en) | 2018-06-05 | 2019-12-12 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
PE20210182A1 (es) | 2018-06-20 | 2021-01-29 | Albireo Ab | Modificaciones de cristales de odexibat |
US11801226B2 (en) | 2018-06-20 | 2023-10-31 | Albireo Ab | Pharmaceutical formulation of odevixibat |
US11007142B2 (en) | 2018-08-09 | 2021-05-18 | Albireo Ab | Oral cholestyramine formulation and use thereof |
US11549878B2 (en) | 2018-08-09 | 2023-01-10 | Albireo Ab | In vitro method for determining the adsorbing capacity of an insoluble adsorbant |
US10722457B2 (en) | 2018-08-09 | 2020-07-28 | Albireo Ab | Oral cholestyramine formulation and use thereof |
US10975045B2 (en) | 2019-02-06 | 2021-04-13 | Aibireo AB | Benzothiazepine compounds and their use as bile acid modulators |
CN113453753A (zh) | 2019-02-06 | 2021-09-28 | 阿尔比里奥公司 | 苯并硫氮杂环庚三烯化合物及其用作胆汁酸调节剂的用途 |
MX2021008981A (es) | 2019-02-06 | 2021-09-08 | Albireo Ab | Compuestos de benzotiadiazepina y su uso como moduladores del acido biliar. |
US10941127B2 (en) | 2019-02-06 | 2021-03-09 | Albireo Ab | Benzothiadiazepine compounds and their use as bile acid modulators |
EP3861074A2 (de) | 2019-09-26 | 2021-08-11 | Sony Group Corporation | Polymere tandemfarbstoffe mit linkergruppen |
CN114761080A (zh) | 2019-12-04 | 2022-07-15 | 阿尔比里奥公司 | 苯并硫杂(二)氮杂环庚三烯化合物及其作为胆汁酸调节剂的用途 |
TW202134218A (zh) | 2019-12-04 | 2021-09-16 | 瑞典商艾爾比瑞歐公司 | 苯并噻氮呯化合物及其作為膽酸調節劑之用途 |
TW202134221A (zh) | 2019-12-04 | 2021-09-16 | 瑞典商艾爾比瑞歐公司 | 苯并噻二氮呯化合物及其作為膽酸調節劑之用途 |
KR20220109450A (ko) | 2019-12-04 | 2022-08-04 | 알비레오 에이비 | 벤조티아(디)아제핀 화합물 및 담즙산 조절제로서의 이의 용도 |
US11014898B1 (en) | 2020-12-04 | 2021-05-25 | Albireo Ab | Benzothiazepine compounds and their use as bile acid modulators |
TW202134222A (zh) | 2019-12-04 | 2021-09-16 | 瑞典商艾爾比瑞歐公司 | 苯并噻(二)氮呯化合物及其作為膽酸調節劑之用途 |
EP4069359B1 (de) | 2019-12-04 | 2024-01-03 | Albireo AB | Benzothia(di)azepinverbindungen und ihre verwendung als gallensäuremodulatoren |
AR120679A1 (es) | 2019-12-04 | 2022-03-09 | Albireo Ab | Compuestos de benzoti(di)azepina y su uso como moduladores ácido biliar |
WO2021110886A1 (en) | 2019-12-04 | 2021-06-10 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
CN114761018A (zh) | 2019-12-04 | 2022-07-15 | 阿尔比里奥公司 | 苯并硫杂二氮杂环庚三烯化合物及其作为胆汁酸调节剂的用途 |
JP2023537285A (ja) | 2020-08-03 | 2023-08-31 | アルビレオ・アクチボラグ | ベンゾチア(ジ)アゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用 |
JP2023549226A (ja) | 2020-11-12 | 2023-11-22 | アルビレオ エービー | 進行性家族性肝内胆汁うっ滞症(pfic)を処置するためのオデビキシバット |
BR112023010799A2 (pt) | 2020-12-04 | 2023-10-03 | Albireo Ab | Compostos de benzotia(di)azepina e seus usos como moduladores de ácidos biliares |
WO2023237728A1 (en) | 2022-06-09 | 2023-12-14 | Albireo Ab | Treating hepatitis |
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AU664059B2 (en) * | 1991-12-20 | 1995-11-02 | Hoechst Aktiengesellschaft | Ethylenically unsaturated bile acid derivatives, processes for their preparation and precursors |
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ES2096150T3 (es) * | 1992-07-22 | 1997-03-01 | Hoechst Ag | Copolimeros vinilicos reticulados, procedimiento para su preparacion, asi como el empleo de estos compuestos. |
DE4234537A1 (de) * | 1992-10-14 | 1994-04-21 | Hoechst Ag | Zubereitung, enthaltend Insulin und polymere Gallensäure |
JPH06321785A (ja) * | 1993-05-12 | 1994-11-22 | Sekisui Chem Co Ltd | 胆汁酸腸管吸収抑制剤 |
JPH06329543A (ja) * | 1993-05-20 | 1994-11-29 | Sekisui Chem Co Ltd | 経口コレステロール低下剤 |
US5607669A (en) * | 1994-06-10 | 1997-03-04 | Geltex Pharmaceuticals, Inc. | Amine polymer sequestrant and method of cholesterol depletion |
-
1996
- 1996-08-19 DE DE19633268A patent/DE19633268A1/de not_active Withdrawn
-
1997
- 1997-07-25 EP EP97940028A patent/EP0918544A2/de not_active Withdrawn
- 1997-07-25 CA CA002263671A patent/CA2263671A1/en not_active Abandoned
- 1997-07-25 WO PCT/EP1997/004049 patent/WO1998007449A2/de not_active Application Discontinuation
- 1997-07-25 JP JP10510319A patent/JP2000517356A/ja active Pending
Non-Patent Citations (1)
Title |
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See references of WO9807449A2 * |
Also Published As
Publication number | Publication date |
---|---|
WO1998007449A2 (de) | 1998-02-26 |
CA2263671A1 (en) | 1998-02-26 |
JP2000517356A (ja) | 2000-12-26 |
WO1998007449A3 (de) | 1998-06-25 |
DE19633268A1 (de) | 1998-02-26 |
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