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WO2000048577A1 - Medicament destine au traitement ou a la prevention du cancer de l'intestin - Google Patents

Medicament destine au traitement ou a la prevention du cancer de l'intestin Download PDF

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Publication number
WO2000048577A1
WO2000048577A1 PCT/EP2000/000549 EP0000549W WO0048577A1 WO 2000048577 A1 WO2000048577 A1 WO 2000048577A1 EP 0000549 W EP0000549 W EP 0000549W WO 0048577 A1 WO0048577 A1 WO 0048577A1
Authority
WO
WIPO (PCT)
Prior art keywords
medicament according
active substance
medicament
udca
release
Prior art date
Application number
PCT/EP2000/000549
Other languages
German (de)
English (en)
Inventor
Norbert Otterbeck
Original Assignee
Dr. Falk Pharma Gmbh
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 Dr. Falk Pharma Gmbh filed Critical Dr. Falk Pharma Gmbh
Publication of WO2000048577A1 publication Critical patent/WO2000048577A1/fr

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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • the invention relates to pharmaceuticals, in particular pharmaceuticals with a controlled release profile, with ursodeoxycholic acid (UDCA), pharmaceutically acceptable salts or derivatives thereof as an active ingredient.
  • UDCA ursodeoxycholic acid
  • the drugs are used to treat or prevent cancer of the large intestine.
  • the active substance in the medicaments according to the invention is only released in the terminal ileum and / or large intestine, preferably in a controlled manner, so that the active substance is only slightly absorbed.
  • UDCA thus does not act systemically but topically directly at the site of the release.
  • UDCA UDCA with a controlled release profile
  • the pharmaceutical forms described there are described as being suitable both for the treatment of liver diseases and for the prevention of colon cancer. Since the active substance for the treatment of liver diseases has to be absorbed from the intestine in order to be able to reach the site of action, the release is controlled in such a way that the active substance is quickly released in the duodenum shortly after leaving the stomach. Since UDCA is very effectively absorbed in the duodenum, high plasma levels are achieved with the pharmaceutical formulations described there, so that none or only a small part of the UDCA passes into the large intestine.
  • WO 97/34608 describes the use of UDCA and a non-steroidal anti-inflammatory active ingredient to prevent the reappearance of colorectal adenomas.
  • parenteral formulations orally administrable formulations in liquid or solid form are also described, the latter also being able to be enteric-coated, so that the active compounds are systemically active either directly or after absorption in the stomach or upper small intestine.
  • EP 0 510 404 describes pharmaceutical formulations containing salts of bile acids which are coated with two layers.
  • the first layer consisting of hydroxypropylmethyl cellulose, polyethylene glycol, titanium dioxide and talc serves as an auxiliary layer to ensure optimal application of the second layer.
  • the second layer consists of an enteric coating.
  • WO 97/18816 describes derivatives of UDCA (e.g. UDCA-3 sulfate, UDCA-7 sulfate, UDCA-3, 7 disulfate), which are also said to be suitable for the prevention of colon cancer.
  • UDCA e.g. UDCA-3 sulfate, UDCA-7 sulfate, UDCA-3, 7 disulfate
  • absorption in the small intestine is prevented by the sulfation of the hydroxyl groups at position 7, so that the majority of the UDCA derivatives reach the large intestine. It has not yet been investigated whether these UDCA derivatives have a positive effect on colon cancer prevention.
  • the object of the invention is therefore to provide medicinal products for the treatment or prevention of colon cancer which do not have the disadvantages of the prior art.
  • this object is achieved by a medicament, in particular by a medicament with a controlled release profile, which contains UDCA, a pharmaceutically acceptable salt or a derivative thereof as the active ingredient characterized in that the drug comprises from the inside out:
  • an active substance-containing core which is designed such that the active substance is released in the terminal ileum and / or in the large intestine and
  • the medicament is advantageously either designed so that it has an active substance-containing core in which the active substance is homogeneously distributed and which is surrounded by a release-controlling layer or, particularly preferably, that the active substance-containing core is a matrix core in which the active substance is in a matrix polymer is embedded.
  • the presence of a release-controlling layer is optional.
  • UDCA is not or only very slightly absorbed in the terminal ileum and large intestine
  • the active ingredient comes into direct contact with the tissue to be treated through the release-controlling polymer matrix in the core and / or the release-controlling layer between the core and enteric coating act so topically, that is, not via the bloodstream.
  • UDCA a pharmaceutically acceptable salt or a derivative thereof for the topical treatment or prevention of colon cancer is also made available, that is to say to a large extent excluding the systemic effect.
  • UDCA when administered systemically, is used to prevent Colon cancer can be used, the prior art does not describe a UDCA-containing pharmaceutical formulation that only releases the active ingredient in the large intestine and is therefore topical due to the very low absorption in the large intestine.
  • large intestine in the context of this description refers to the cecum, the ascending colon, transverse colon, descending colon, the sigmoid and the rectum.
  • UDCA is not only systemically effective in the treatment or prevention of colon cancer, but that UDCA is also extremely effective when administered topically in the colon.
  • a systemic effect does not occur or only to a very small extent, since in the areas in which the active substance is released no or only small amounts of the active substance are absorbed.
  • the effectiveness of UDCA is directly related to its concentration in the large intestine. Due to the topical administration and the greatly reduced absorption of the active ingredient, possible side effects, which are necessary after a very long period of use, as is necessary for treatment or prevention therapy.
  • the medicaments according to the invention contain UDCA or a pharmaceutically acceptable salt or derivative thereof as the active ingredient.
  • the pharmaceuticals according to the invention do not release the active ingredient in the stomach or upper part of the small intestine, but only in the terminal ileum and / or large intestine, so that as little as possible of the active ingredient is absorbed and thus the highest possible concentration of the active ingredient in the large intestine is achieved.
  • the release of the active ingredient in the terminal ileum and / or large intestine is achieved in that it releases the active ingredient in a delayed or controlled manner.
  • the medicament is preferably formulated as tablets or pellets which are coated with an enteric lacquer and / or a release-controlling layer, so that an early release of the active ingredient is prevented.
  • the pellets can in turn be filled into gelatin capsules or pressed into pellet tablets.
  • WO 92/14452 describes granules which consist of an active substance-containing core which is coated with (meth) acrylate and / or (meth) acrylic acid lacquers. These granules are filled into gelatin capsules and the glatin capsules are then coated with these varnishes so that they are enteric-coated.
  • WO 91/16042 describes granules with a diameter of not more than 5 mm, which are covered with two shells.
  • One shell consists of a polymer which is soluble as a function of the pH and dissolves at a pH greater than 5.0
  • the second shell consists of one or more polymers which are insoluble or only slightly soluble in gastrointestinal fluid.
  • the active substances can be released in the small and / or large intestine.
  • WO 91/07949 describes pharmaceutical formulations which contain an active ingredient and amorphous amylose in a core which is coated with a film-forming cellulose or another polymer. This ensures that the active ingredient is released in the large intestine.
  • EP 0 621 032 describes active substance-containing cores which are coated with a release-delaying layer, an overlying semi-permeable layer and optionally with an outer layer made of an enteric coating, so that the active substance is only released in the large intestine.
  • the formulations according to the invention are coated with an enteric coating.
  • This coating should only dissolve after the formulation has left the stomach.
  • Corresponding coatings are described in the prior art, for example in the above publications.
  • Enteric coatings which are composed of polymers or copolymers derived from (meth) acrylates are particularly preferred.
  • a pellet formulation is particularly preferred according to the invention since, in contrast to a tablet formulation, it reproducibly spreads the active ingredient over large areas of the large intestine.
  • mixtures according to the invention from two or more pellet formulations with different release behavior in a mixture ratio suitable for the treatment or prevention of colon cancer are particularly preferred.
  • a pellet type whose active ingredient release already begins in the terminal ileum can be combined with a pellet type whose active ingredient release only begins in the transverse colon, mixed and filled into a gelatin capsule or pressed in a pellet tablet.
  • An orally administrable pellet formulation in which the active ingredient is embedded in the pellet core in a polymer matrix is particularly preferred.
  • Suitable polymers which form the matrix are all polymers known in the prior art and usable for this purpose (K.H. Bauer K.-H. Frömming, C. 5.3: Pharmaceutical Technology, Georg Thieme Verlag Stuttgart, New York (1989)).
  • the matrix-forming polymer is preferably selected from the group consisting of poly (ethyl acrylate, methyl acrylate) and poly (ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride).
  • Such copolymers are, for example, the commercial products Eudragit NE 30 D and Eudragit NE 40 D.
  • pellet formulations are particularly preferred in which a further layer of water-soluble cellulose derivatives such as, for example, is located between the active substance core and the enteric layer
  • Hydroxypropylmethylcellulose methylcellulose, sodium carboxymethylcellulose or ethylcellulose «and / or depending on the pH value soluble polymers of acrylic acid (carbomers).
  • the enteric coating of the tablets or pellets is preferably based on water-insoluble and / or pH-dependent water-soluble polyacrylates.
  • Suitable polyacrylates are e.g. Poly (ethyl acrylate, methyl acrylate) 1: 1, poly (methacrylic acid, methyl methacrylate) 1: 2,
  • the controlled release profile can be varied in a manner known per se to the person skilled in the art so that after reaching the terminal ileum or the colon, the active ingredient for Example is released immediately or evenly over a certain period of time.
  • the medicaments according to the invention can contain further customary auxiliaries and excipients, as are known in the prior art and are described, for example, in K.H. Frömming, C. 4.5: Pharmaceutical Technology, Georg Thieme Verlag Stuttgart, New York (1989).
  • the pharmaceutical formulations described above allow topical use of UDCA and thus the active substance is only released specifically in the terminal ileum and / or large intestine
  • the medicaments according to the invention for treatment or prevention of the colorectal cancer to reduce the necessary amount of active ingredient.
  • a significant advantage of the specific release in the terminal ileum and / or large intestine is that even with an undiminished amount of active ingredient, the absorption of the active ingredient takes place only to a very small extent and thus side effects that could occur if the medication was taken over a very long time. be reduced.
  • the pharmaceuticals according to the invention can therefore contain the active ingredient in an amount as is also present in the already known UDCA-containing pharmaceuticals. If necessary for the treatment or prevention of colon cancer, a higher amount of UDCA than previously described can also be used due to the very low absorption due to the formulation according to the invention.
  • the preferred dosage of the medicinal substances when administered by the medicaments according to the invention is 1 to 100 mg / kg of body weight per day, particularly preferred are 5 to 50 mg / kg of body weight per day. Accordingly, a single dose of the medicament according to the invention preferably contains 100 mg to 1000 mg, particularly preferably 150-500 mg, of active ingredient.
  • Example for matrix pellet cores 1.
  • I-IV are mixed and moistened with V and kneaded intensively. VI is then sprinkled in. The moist mass is pressed through an extruder with the die hole 1 mm, cut into pieces approx. 1 mm long and rounded in a spheronizer. The pellets are dried at approx. 60 ° C.
  • the pellets are coated with a solution of 30 g hydroxypropylmethyl cellulose in 300 ml water (protective cover).
  • the pellets are coated with the following solution gastro-resistant:
  • I-IV are mixed and moistened with V and kneaded intensively. VI is then sprinkled in. The moist mass is passed through a sieve with a mesh size of 1 mm. The resulting granulate is dried at approx. 60 ° C.
  • the granules are used as the outer phase
  • the mixture is pressed into tablets of 545 mg.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention repose sur la découverte surprenante que l'on peut utiliser l'acide ursodésoxycholique en administration locale pour traiter ou prévenir le cancer colique. Elle concerne donc un médicament formulé de façon que l'acide ursodésoxycholique ne soit libéré que dans l'iléon terminal et/ou le colon. De cette manière, le principe actif n'est que faiblement résorbé et agit non pas de façon systémique mais locale, directement au niveau du site de libération.
PCT/EP2000/000549 1999-02-15 2000-01-25 Medicament destine au traitement ou a la prevention du cancer de l'intestin WO2000048577A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19906290.0 1999-02-15
DE19906290A DE19906290A1 (de) 1999-02-15 1999-02-15 Arzneimittel zur Behandlung bzw. Prävention von Darmkrebs

Publications (1)

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WO2000048577A1 true WO2000048577A1 (fr) 2000-08-24

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DE (1) DE19906290A1 (fr)
WO (1) WO2000048577A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1317925A1 (fr) * 2001-12-06 2003-06-11 ISTITUTO BIOCHIMICO ITALIANO GIOVANNI LORENZINI S.p.A. Microgranules de l'acide ursodesoxycholique
WO2008130234A1 (fr) * 2007-04-19 2008-10-30 Disphar International B.V. Composition à dose élevée d'acide ursodésoxycholique
EP2208497A1 (fr) * 2009-01-15 2010-07-21 Charité-Universitätsmedizin Berlin (Charité) Utilisation d'acide ursodeoxycholique (UDCA) pour améliorer la condition de santé générale d'un patient ayant une tumeur
US9101544B2 (en) 2006-08-30 2015-08-11 Jagotec Ag Controlled release nisoldipine compositions

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100368936B1 (ko) * 2000-10-04 2003-01-24 주식회사 대웅 우루소데옥시콜린산을 함유한 환경호르몬 독성의 예방 및치료제
US20050226926A1 (en) 2002-07-25 2005-10-13 Pfizer Inc Sustained-release tablet composition of pramipexole
SI1789021T1 (sl) 2004-08-13 2012-02-29 Boehringer Ingelheim Int Tabletna formulacija s podaljšanim sproščanjem, ki vsebuje pramipeksol ali njegovo farmacevtsko sprejemljivo sol
AU2013202344B2 (en) * 2006-08-30 2014-07-17 Jagotec Ag Controlled release oral dosage formulations comprising a core and one or more barrier layers
US20110268794A1 (en) * 2009-01-09 2011-11-03 Camilleri Michael L Methods and materials for delivering bile acids
EP2465496A1 (fr) * 2010-11-22 2012-06-20 Salmon Pharma GmbH Composition pharmaceutique anti-azidotique

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2036558A (en) * 1978-12-15 1980-07-02 Lehner Ag Bile acid containing compositions
EP0509335A1 (fr) * 1991-04-12 1992-10-21 ALFA WASSERMANN S.p.A. Formulations pharmaceutiques gastrorésistantes pour l'administration par voie orale d'acides biliaires
EP0625353A1 (fr) * 1993-05-18 1994-11-23 ISTITUTO BIOCHIMICO ITALIANO GIOVANNI LORENZINI S.p.A. Composition pharmaceutique à libération lente contenant un acide biliaire comme agent actif
DE19645044A1 (de) * 1996-10-31 1998-05-07 Falk Pharma Gmbh Verwendung von Ursodeoxycholsäure zur topischen Behandlung von Entzündungserkrankungen der Schleimhäute

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1245889B (it) * 1991-04-12 1994-10-25 Alfa Wassermann Spa Formulazioni farmaceutiche per uso orale gastroresistenti contenenti sali di acidi biliari.
IT1249686B (it) * 1991-07-22 1995-03-09 Boniscontro E Gazzone S R L Preparazioni farmaceutiche orali, a base di acidi biliari, a cessione protratta e controllata con le quali e' possibile adottare una sola somministrazione giornaliera
US5234697A (en) * 1992-06-22 1993-08-10 Digestive Care Inc. Compositions of gastric acid-resistant microspheres containing salts of bile acids
US5415872A (en) * 1992-06-22 1995-05-16 Digestive Care Inc. Compositions of gastric acid-resistant microspheres containing salts of bile acids
US5763435A (en) * 1995-11-21 1998-06-09 Children's Hospital Medical Center Sulfate conjugates of ursodeoxycholic acid, and their beneficial use in inflammatory disorders
JP2000507938A (ja) * 1996-03-22 2000-06-27 マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチ 結腸直腸の化学的保護のためのウルソデオキシコール酸化合物及びｎｓａｉｄの組合せ
US5843929A (en) * 1996-03-22 1998-12-01 Mayo Foundation For Medical Education And Research Chemoprevention of metachronous adenomatous colorectal polyps
US6214378B1 (en) * 1996-08-02 2001-04-10 Hisamitsu Pharmaceutical Co., Inc. Capsules for oral preparations and capsule preparations for oral administration

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2036558A (en) * 1978-12-15 1980-07-02 Lehner Ag Bile acid containing compositions
EP0509335A1 (fr) * 1991-04-12 1992-10-21 ALFA WASSERMANN S.p.A. Formulations pharmaceutiques gastrorésistantes pour l'administration par voie orale d'acides biliaires
EP0625353A1 (fr) * 1993-05-18 1994-11-23 ISTITUTO BIOCHIMICO ITALIANO GIOVANNI LORENZINI S.p.A. Composition pharmaceutique à libération lente contenant un acide biliaire comme agent actif
DE19645044A1 (de) * 1996-10-31 1998-05-07 Falk Pharma Gmbh Verwendung von Ursodeoxycholsäure zur topischen Behandlung von Entzündungserkrankungen der Schleimhäute

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BATTA AK, ET AL.: "Enrichment of the more hydrophilic bile acid ursodeoxycholic acid in the fecal water-soluble fraction after feeding to rats with colon polyps", CANCER RESEARCH, vol. 58, no. 8, 1998, ISSN 0008-5472, pages 1684 - 1687, XP002140692 *
EARNEST DL, ET AL.: "Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid", CANCER RESEARCH, vol. 54, no. 19, 1994, ISSN 0008-5472, pages 5071 - 5074, XP002140691 *
RODRIGUES CMP, ET AL.: "The site-specific delivery of ursodeoxycholic acid to the rat colon by sulfate conjugation", GASTROENTEROLOGY, vol. 109, no. 6, 1995, ISSN 0016-5085, pages 1835 - 1844, XP000644482 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1317925A1 (fr) * 2001-12-06 2003-06-11 ISTITUTO BIOCHIMICO ITALIANO GIOVANNI LORENZINI S.p.A. Microgranules de l'acide ursodesoxycholique
US9101544B2 (en) 2006-08-30 2015-08-11 Jagotec Ag Controlled release nisoldipine compositions
US9622980B2 (en) 2006-08-30 2017-04-18 Jagotec Ag Controlled release compositions
WO2008130234A1 (fr) * 2007-04-19 2008-10-30 Disphar International B.V. Composition à dose élevée d'acide ursodésoxycholique
EP2208497A1 (fr) * 2009-01-15 2010-07-21 Charité-Universitätsmedizin Berlin (Charité) Utilisation d'acide ursodeoxycholique (UDCA) pour améliorer la condition de santé générale d'un patient ayant une tumeur

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