WO2001076531A2 - Promedicaments contenant un acide biliaire et presentant une meilleure biodisponibilite - Google Patents

Promedicaments contenant un acide biliaire et presentant une meilleure biodisponibilite Download PDF

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Publication number
WO2001076531A2
WO2001076531A2 PCT/US2001/011327 US0111327W WO0176531A2 WO 2001076531 A2 WO2001076531 A2 WO 2001076531A2 US 0111327 W US0111327 W US 0111327W WO 0176531 A2 WO0176531 A2 WO 0176531A2
Authority
WO
WIPO (PCT)
Prior art keywords
compound
prodrug
group
bile acid
agent
Prior art date
Application number
PCT/US2001/011327
Other languages
English (en)
Other versions
WO2001076531A3 (fr
Inventor
James E. Polli
Andrew Coop
Dean Y. Maeda
Kimberley A. Lentz
Original Assignee
University Of Maryland, Baltimore
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 University Of Maryland, Baltimore filed Critical University Of Maryland, Baltimore
Priority to CA002405151A priority Critical patent/CA2405151A1/fr
Priority to JP2001574050A priority patent/JP2003530329A/ja
Priority to AU2001253226A priority patent/AU2001253226B2/en
Priority to US10/240,859 priority patent/US20030212051A1/en
Priority to AU5322601A priority patent/AU5322601A/xx
Priority to EP01926709A priority patent/EP1267898A4/fr
Publication of WO2001076531A2 publication Critical patent/WO2001076531A2/fr
Publication of WO2001076531A3 publication Critical patent/WO2001076531A3/fr
Priority to AU2006202213A priority patent/AU2006202213A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
    • 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
    • A61K47/51—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 non-active ingredient being a modifying agent
    • A61K47/54—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 non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/554—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 non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton

Definitions

  • the prodrug is administered orally to an animal or human. It is a
  • the intestinal bile acid transporter binds to the
  • Figure ID generalizes the synthesis of acyclovir valyldeoxycholate.
  • Vydac analytical column (C 18 , 300 A, 5 ⁇ m, 4.6 x 250 mm) equipped with a
  • concentration of acyclovir valylchenodeoxycholate, 1, varies between 10 ⁇ M and 400
  • mg proteinV ⁇ M is estimated using linear regression. Control uptake studies are also possible.
  • compositions can be used along with the prodrugs.
  • alendronate etidronate disodium
  • pamidronate risedronate
  • tiludronate etidronate disodium
  • alendronate etidronate disodium
  • pamidronate pamidronate
  • risedronate tiludronate
  • metformin anti-diabetics
  • celecoxib celecoxib, refecoxib (COX-2 inhibitors)

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Botany (AREA)
  • Epidemiology (AREA)
  • Steroid Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

De nombreux composés présentent une biodisponibilité médiocre ou variable du fait de la difficulté d'absorption du composé dans l'intestin grêle. La conjugaison du composé avec l'acide biliaire pour obtenir un promédicament augmente la biodisponibilité du composé et/ou réduit la variabilité de la biodisponibilité du composé du fait du transport actif du promédicament par le transporteur de l'acide biliaire dans l'intestin et du fait du caractère lipophile accru du composé. Un exemple de promédicament contenant l'acide biliaire est l'acyclovir valylchénodésoxycholate, la valine étant le groupe de liaison. Un autre exemple de ce type de promédicament est l'amide d'acide cholique aténolol.
PCT/US2001/011327 2000-04-07 2001-04-06 Promedicaments contenant un acide biliaire et presentant une meilleure biodisponibilite WO2001076531A2 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CA002405151A CA2405151A1 (fr) 2000-04-07 2001-04-06 Promedicaments contenant un acide biliaire et presentant une meilleure biodisponibilite
JP2001574050A JP2003530329A (ja) 2000-04-07 2001-04-06 増大したバイオアベイラビリティを有する胆汁酸含有プロドラッグ
AU2001253226A AU2001253226B2 (en) 2000-04-07 2001-04-06 Bile acid containing prodrugs with enhanced bioavailability
US10/240,859 US20030212051A1 (en) 2001-04-06 2001-04-06 Bile acid containing prodrugs with enhanced bioavailabilty
AU5322601A AU5322601A (en) 2000-04-07 2001-04-06 Bile acid containing prodrugs with enhanced bioavailability
EP01926709A EP1267898A4 (fr) 2000-04-07 2001-04-06 Promedicaments contenant un acide biliaire et presentant une meilleure biodisponibilite
AU2006202213A AU2006202213A1 (en) 2000-04-07 2006-05-25 Bile acid containing prodrugs with enhanced bioavailability

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US19585400P 2000-04-07 2000-04-07
US60/195,854 2000-04-07
US26990601P 2001-02-21 2001-02-21
US60/269,906 2001-02-21

Publications (2)

Publication Number Publication Date
WO2001076531A2 true WO2001076531A2 (fr) 2001-10-18
WO2001076531A3 WO2001076531A3 (fr) 2002-02-14

Family

ID=26891401

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/011327 WO2001076531A2 (fr) 2000-04-07 2001-04-06 Promedicaments contenant un acide biliaire et presentant une meilleure biodisponibilite

Country Status (5)

Country Link
EP (1) EP1267898A4 (fr)
JP (1) JP2003530329A (fr)
AU (3) AU2001253226B2 (fr)
CA (1) CA2405151A1 (fr)
WO (1) WO2001076531A2 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1343805A1 (fr) * 2000-10-06 2003-09-17 Xenoport, Inc. Composes derives d'acide biliaire assurant des concentrations systemiques prolongees de medicaments apres administration par voie orale
EP1358200A2 (fr) * 2000-10-06 2003-11-05 Xenoport, Inc. Composes derives des acides biliaires pouvant ameliorer l'absorption orale et la biodisponibilite systemique de medicaments
US6984634B2 (en) 2000-10-06 2006-01-10 Xenoport, Inc. Bile-acid conjugates for providing sustained systemic concentrations of drugs
JP2006513247A (ja) * 2003-01-13 2006-04-20 ブラッコ・イメージング・ソシエタ・ペル・アチオニ 医薬品化合物のための改善されたリンカー
JP2009530399A (ja) * 2006-03-22 2009-08-27 シンデクサ ファーマシューティカルズ コーポレーション Ｅｒストレスに関連する疾病の治療のための化合物及び方法
US10350169B2 (en) 2014-10-31 2019-07-16 University Of Utah Research Foundation Compositions and methods for bile acid particles

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRPI0418651A (pt) * 2004-08-02 2007-05-29 Ambrilia Biopharma Inc compostos com base em lisina
JP5201546B2 (ja) * 2008-01-18 2013-06-05 学校法人近畿大学 Ｎ‐アセチルシステイン抱合型胆汁酸、それを含有する医薬組成物及びその製造方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993025192A1 (fr) * 1992-06-12 1993-12-23 Cortecs Limited Compositions pharmaceutiques contenant des anti-inflammatoires non steroidiens et des acides biliaires

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPO912997A0 (en) * 1997-09-11 1997-10-02 Commonwealth Scientific And Industrial Research Organisation Antiviral agents
GB9907048D0 (en) * 1999-03-27 1999-05-19 Karobio Ab Novel glucocorticoid receptor ligands for the treatment of meta bolic disorders
ATE363074T1 (de) * 1999-09-14 2007-06-15 Xenoport Inc Substrate und screeningverfahren für transportproteine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993025192A1 (fr) * 1992-06-12 1993-12-23 Cortecs Limited Compositions pharmaceutiques contenant des anti-inflammatoires non steroidiens et des acides biliaires

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS [Online] PONZ DE LEON ET AL.: 'Intestinal solubilization, adsorption, pharmacokinetics and bioavilability of chenodeoxycholic acid', XP002947962 Retrieved from ACS Database accession no. 1981:20322 & EUR. J. CLIN. INVEST. vol. 10, no. 4, 1980, pages 261 - 271 *
DATABASE CAPLUS [Online] SUTTON ET AL.: 'Comparison of the effect of dietary cholesterol on bile acid synthesis in isolated hepatocytes in suspension and in culture', XP002947963 Retrieved from ACS Database accession no. 1988:527832 & BIOCHEM. SOC. TRANS. vol. 16, no. 6, 1988, pages 1001 - 1002 *
DATABASE CAPLUS [Online] VAN BERGE-HENEGOUWEN ET AL.: 'Pharmacology of chenodeoxycholic acid. II. Absorption and metabolism', XP002947964 Retrieved from ACS Database accession no. 1977:496181 & GASTROENTEROLOGY vol. 73, no. 2, 1977, pages 300 - 309 *
See also references of EP1267898A2 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1343805A1 (fr) * 2000-10-06 2003-09-17 Xenoport, Inc. Composes derives d'acide biliaire assurant des concentrations systemiques prolongees de medicaments apres administration par voie orale
EP1358200A2 (fr) * 2000-10-06 2003-11-05 Xenoport, Inc. Composes derives des acides biliaires pouvant ameliorer l'absorption orale et la biodisponibilite systemique de medicaments
EP1343805A4 (fr) * 2000-10-06 2005-07-20 Xenoport Inc Composes derives d'acide biliaire assurant des concentrations systemiques prolongees de medicaments apres administration par voie orale
EP1358200A4 (fr) * 2000-10-06 2005-07-20 Xenoport Inc Composes derives des acides biliaires pouvant ameliorer l'absorption orale et la biodisponibilite systemique de medicaments
US6984634B2 (en) 2000-10-06 2006-01-10 Xenoport, Inc. Bile-acid conjugates for providing sustained systemic concentrations of drugs
US7144877B2 (en) 2000-10-06 2006-12-05 Xenoport, Inc. Bile-acid derived compounds for enhancing oral absorption and systemic bioavailability of drugs
US7598235B2 (en) 2000-10-06 2009-10-06 Xenoport, Inc. Bile-acid conjugates for providing sustained systemic concentrations of drugs
US7678782B2 (en) 2000-10-06 2010-03-16 Xenoport, Inc. Bile-acid derived compounds for enhancing oral absorption and systemic bioavailability of drugs
JP2006513247A (ja) * 2003-01-13 2006-04-20 ブラッコ・イメージング・ソシエタ・ペル・アチオニ 医薬品化合物のための改善されたリンカー
US7989417B2 (en) 2003-01-13 2011-08-02 Bracco Imaging S.P.A. Linkers for radiopharmaceutical compounds
JP2009530399A (ja) * 2006-03-22 2009-08-27 シンデクサ ファーマシューティカルズ コーポレーション Ｅｒストレスに関連する疾病の治療のための化合物及び方法
US10350169B2 (en) 2014-10-31 2019-07-16 University Of Utah Research Foundation Compositions and methods for bile acid particles

Also Published As

Publication number Publication date
JP2003530329A (ja) 2003-10-14
AU2001253226B2 (en) 2006-06-08
AU5322601A (en) 2001-10-23
WO2001076531A3 (fr) 2002-02-14
CA2405151A1 (fr) 2001-10-18
AU2006202213A1 (en) 2006-06-15
EP1267898A2 (fr) 2003-01-02
EP1267898A4 (fr) 2006-02-01

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