NO20004998L - Fettsyrederivater av gallesyrer og gallesyrederivater - Google Patents

Fettsyrederivater av gallesyrer og gallesyrederivater

Info

Publication number: NO20004998L
Authority: NO; Norway
Prior art keywords: bile; acid derivatives; acid; fatty acid; bile salt
Prior art date: 1998-04-08

Application number

NO20004998A

Other languages

English (en)

Other versions

NO20004998D0 (no

NO316875B1 (no

Inventor

Tuvia Gilat

Original Assignee

Galmed Int Ltd

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.)

1998-04-08

Filing date

2000-10-04

Publication date

2000-12-06

2000-10-04 Application filed by Galmed Int Ltd filed Critical Galmed Int Ltd

2000-10-04 Publication of NO20004998D0 publication Critical patent/NO20004998D0/no

2000-12-06 Publication of NO20004998L publication Critical patent/NO20004998L/no

2004-06-07 Publication of NO316875B1 publication Critical patent/NO316875B1/no

Links

HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 title abstract 5
239000003613 bile acid Substances 0.000 title abstract 5
229940053200 antiepileptics fatty acid derivative Drugs 0.000 title 1
239000003833 bile salt Substances 0.000 abstract 4
235000014113 dietary fatty acids Nutrition 0.000 abstract 3
229930195729 fatty acid Natural products 0.000 abstract 3
239000000194 fatty acid Substances 0.000 abstract 3
150000004665 fatty acids Chemical class 0.000 abstract 3
206010003210 Arteriosclerosis Diseases 0.000 abstract 1
208000011775 arteriosclerosis disease Diseases 0.000 abstract 1
210000000941 bile Anatomy 0.000 abstract 1
125000004432 carbon atom Chemical group C* 0.000 abstract 1
201000001883 cholelithiasis Diseases 0.000 abstract 1
230000021615 conjugation Effects 0.000 abstract 1
201000010099 disease Diseases 0.000 abstract 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
150000004671 saturated fatty acids Chemical class 0.000 abstract 1
235000003441 saturated fatty acids Nutrition 0.000 abstract 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- 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
- 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
- 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
- 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
- A61P9/10—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
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Gastroenterology & Hepatology (AREA)
Steroid Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Fats And Perfumes (AREA)

NO20004998A 1998-04-08 2000-10-04 Fettsyrederivater av gallesyrer og gallesyrederivater NO316875B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IL12399898A IL123998A (en)	1998-04-08	1998-04-08	Conjugates of bile salts and pharmaceutical preparations containing them
PCT/IL1999/000173 WO1999052932A1 (en)	1998-04-08	1999-03-25	Fatty acid derivatives of bile acids and bile acid derivatives

Publications (3)

Publication Number	Publication Date
NO20004998D0 NO20004998D0 (no)	2000-10-04
NO20004998L true NO20004998L (no)	2000-12-06
NO316875B1 NO316875B1 (no)	2004-06-07

Family

ID=11071405

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20004998A NO316875B1 (no)	1998-04-08	2000-10-04	Fettsyrederivater av gallesyrer og gallesyrederivater

Country Status (25)

Country	Link
US (3)	US6395722B1 (no)
EP (1)	EP1071702B1 (no)
JP (1)	JP5031942B2 (no)
KR (1)	KR100615560B1 (no)
CN (1)	CN100386339C (no)
AT (1)	ATE222923T1 (no)
AU (1)	AU742944B2 (no)
BR (1)	BRPI9909908B8 (no)
CA (1)	CA2325933C (no)
CZ (1)	CZ300824B6 (no)
DE (1)	DE69902647T2 (no)
DK (1)	DK1071702T3 (no)
EA (1)	EA003392B1 (no)
ES (1)	ES2183526T3 (no)
HU (1)	HU229513B1 (no)
ID (1)	ID26042A (no)
IL (1)	IL123998A (no)
NO (1)	NO316875B1 (no)
NZ (1)	NZ507309A (no)
PL (1)	PL199271B1 (no)
PT (1)	PT1071702E (no)
SI (1)	SI1071702T1 (no)
TR (1)	TR200002876T2 (no)
UA (1)	UA70318C2 (no)
WO (1)	WO1999052932A1 (no)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL142650A (en) *	1998-04-08	2007-06-03	Galmed Int Ltd	Use of bile acid conjugates or bile salts and fatty acids or fatty acids in the preparation of pharmaceuticals for lowering cholesterol, for the treatment of fatty liver and for the treatment of hyperglycemia and diabetes
IL123998A (en) *	1998-04-08	2004-09-27	Galmed Int Ltd	Conjugates of bile salts and pharmaceutical preparations containing them
US20030083231A1 (en) *	1998-11-24	2003-05-01	Ahlem Clarence N.	Blood cell deficiency treatment method
US8975246B2 (en)	2001-04-17	2015-03-10	Galmed Research And Development Ltd.	Bile acid or bile salt fatty acid conjugates
US7053076B2 (en)	2001-08-29	2006-05-30	Xenoport, Inc.	Bile-acid derived compounds for enhancing oral absorption and systemic bioavailability of drugs
ITMI20021025A1 (it) *	2002-05-14	2003-11-14	Nicox Sa	Farmaci per il trattamento acuto di disfunzioni del circolo venoso epatico e portale
US20080026077A1 (en) *	2002-11-12	2008-01-31	John Hilfinger	Methods and compositions of gene delivery agents for systemic and local therapy
US7906137B2 (en) *	2004-05-21	2011-03-15	Mediplex Corporation, Korea	Delivery agents for enhancing mucosal absorption of therapeutic agents
WO2007084549A2 (en) *	2006-01-20	2007-07-26	Filiberto Zadini	Drug-eluting stent with atherosclerotic plaques dissolving pharmacological preparation
US8304383B2 (en) *	2005-11-22	2012-11-06	Atheronova Operations, Inc.	Dissolution of arterial plaque
US20090035348A1 (en) *	2005-11-22	2009-02-05	Z & Z Medical Holdings, Inc.	Dissolution of arterial plaque
US20080038385A1 (en) *	2006-03-13	2008-02-14	Nutracea	Therapeutic uses of an anti-cancer composition derived from rice bran
US20070212470A1 (en) *	2006-03-13	2007-09-13	Nutracea	Therapeutic uses of an anti-cancer composition derived from rice bran
US20090305943A1 (en) *	2006-07-18	2009-12-10	Sven Siegel	Cyclodextrin blends with crystal growth inhibitors
WO2008131419A2 (en)	2007-04-23	2008-10-30	Alnylam Pharmaceuticals, Inc.	Glycoconjugates of rna interference agents
US20080287429A1 (en) *	2007-05-15	2008-11-20	Z & Z Medical Holdings, Inc.	Dissolution of Arterial Cholesterol Plaques by Pharmacologically Induced Elevation of Endogenous Bile Salts
PT2182954T (pt) *	2007-07-25	2019-02-06	Univ Graz Medizinische	Utilização de ácidos nor-biliares no tratamento de arteriosclerose
CN101367859B (zh) *	2007-08-17	2011-05-11	中国人民解放军军事医学科学院毒物药物研究所	脂肪酸胆汁酸偶合物及其医药用途
CZ301037B6 (cs) *	2007-09-06	2009-10-21	Vysoká škola chemicko-technologická v Praze	Amidové konjugáty steroidních a žlucových kyselin s D-glukosaminem a zpusob jejich prípravy
AU2008340354B2 (en)	2007-12-04	2014-04-17	Alnylam Pharmaceuticals, Inc.	Folate-iRNA conjugates
CA2910760C (en) *	2007-12-04	2019-07-09	Muthiah Manoharan	Targeting lipids
US20100021538A1 (en) *	2008-02-29	2010-01-28	Youngro Byun	Pharmaceutical compositions containing heparin derivatives
JP5788312B2 (ja)	2008-04-11	2015-09-30	アルニラムファーマスーティカルズインコーポレイテッドＡｌｎｙｌａｍＰｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ．	標的リガンドをエンドソーム分解性成分と組み合わせることによる核酸の部位特異的送達
JP5620392B2 (ja) *	2008-11-03	2014-11-05	タフツユニヴァーシティーＴｕｆｔｓＵｎｉｖｅｒｓｉｔｙ	クロストリジウム・ディフィシレ胞子の発芽および伸長を阻害するための方法および組成物
WO2010086864A1 (en) *	2009-02-02	2010-08-05	Galmed International Ltd.	Methods and compositions for treating alzheimer's disease
GB2480632A (en)	2010-05-25	2011-11-30	Kythera Biopharmaceuticals Inc	Preparation of 12-keto and 12-alpha-hydroxy steroids
CN102115486B (zh) *	2009-12-30	2015-06-03	上海特化医药科技有限公司	一种3-β-花生酰胺基-7α,12α,5β-胆烷-24-羧酸的制备方法
TWI665211B (zh) *	2011-06-16	2019-07-11	美商凱瑟拉生物製藥有限公司	去氧膽酸之組成物及用途及其相關方法
EP3030229B1 (en) *	2013-08-08	2019-03-13	Galmed Research and Development Ltd.	Anti-acne compositions comprising bile acid-fatty acid conjugates
US11571431B2 (en)	2013-12-04	2023-02-07	Galmed Research And Development Ltd	Aramchol salts
TR201909447T4 (tr) *	2013-12-04	2019-07-22	Galmed Res & Development Ltd	Aramkol tuzları.
US20170196891A1 (en) *	2014-06-01	2017-07-13	Galmed Research And Development Ltd.	Fatty acid bile acid conjugates for treatment of lipodystrophy
HRP20192177T1 (hr)	2014-11-10	2020-02-21	Alnylam Pharmaceuticals, Inc.	Rnai pripravci za virus hepatitisa b (hbv) i postupci njihove upotrebe
US10849911B2 (en)	2015-06-10	2020-12-01	Galmed Research And Development Ltd.	Low dose compositions of Aramachol salts
IL243707A0 (en)	2016-01-20	2016-05-01	Galmed Res And Dev Ltd	Treatment to regulate the microbiota in the intestine
CN106496300B (zh) *	2016-10-19	2018-05-18	上海博志研新药物技术有限公司	花生胆酸及其中间体的制备方法
US11197870B2 (en)	2016-11-10	2021-12-14	Galmed Research And Development Ltd	Treatment for hepatic fibrosis
BR112019009509A2 (pt) *	2016-11-10	2019-07-30	Galmed Res And Development Ltd	inibição de fibrose em pacientes com doença hepática gordurosa não alcoólica
US11324820B2 (en)	2017-04-18	2022-05-10	Alnylam Pharmaceuticals, Inc.	Methods for the treatment of subjects having a hepatitis b virus (HBV) infection
US11136347B2 (en)	2017-06-07	2021-10-05	Crystal Pharmaceutical (Suzhou) Co., Ltd.	Crystalline forms of a fatty acid bile acid conjugate, preparation method thereof and use thereof
KR102918289B1 (ko)	2018-08-13	2026-01-28	알닐람 파마슈티칼스 인코포레이티드	B형 간염 바이러스 (HBV) dsRNA 제제 조성물 및 이의 사용 방법
IT202000000328A1 (it)	2020-01-10	2021-07-10	Ice S P A	Metodo di preparazione dell'aramchol
CN114524857B (zh) *	2022-02-22	2023-06-30	中国科学院微生物研究所	胆酸衍生物及其应用
CN116687850A (zh)	2022-02-24	2023-09-05	甘莱制药有限公司	包含环状膦酸酯化合物的药物组合物及其制备方法与用途
WO2023227723A1 (en) *	2022-05-26	2023-11-30	Pharmazell Gmbh	An improved process for the preparation of aramchol and salts thereof

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Publication number	Priority date	Publication date	Assignee	Title
US3856953A (en) *	1973-05-15	1974-12-24	Intellectual Property Dev Corp	Method of treating fatty liver
IT1167479B (it) *	1981-07-24	1987-05-13	Carlo Scolastico	Derivati dell'acido chenodesossicolico
IT1167478B (it) *	1981-07-24	1987-05-13	Carlo Scolastico	Derivati dell'acido ursodesossicolico
DE3930696A1 (de) *	1989-09-14	1991-03-28	Hoechst Ag	Gallensaeurederivate, verfahren zu ihrer herstellung, verwendung als arzneimittel
IL123998A (en) *	1998-04-08	2004-09-27	Galmed Int Ltd	Conjugates of bile salts and pharmaceutical preparations containing them
DE19824123A1 (de) *	1998-05-29	1999-12-02	Hoechst Marion Roussel De Gmbh	Gallensäurederivat, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung

1998
- 1998-04-08 IL IL12399898A patent/IL123998A/en not_active IP Right Cessation
1999
- 1999-03-25 AT AT99912026T patent/ATE222923T1/de active
- 1999-03-25 EP EP99912026A patent/EP1071702B1/en not_active Expired - Lifetime
- 1999-03-25 TR TR2000/02876T patent/TR200002876T2/xx unknown
- 1999-03-25 HU HU0101653A patent/HU229513B1/hu unknown
- 1999-03-25 PT PT99912026T patent/PT1071702E/pt unknown
- 1999-03-25 CN CNB998049034A patent/CN100386339C/zh not_active Expired - Lifetime
- 1999-03-25 SI SI9930142T patent/SI1071702T1/xx unknown
- 1999-03-25 ID IDW20001998A patent/ID26042A/id unknown
- 1999-03-25 PL PL343360A patent/PL199271B1/pl unknown
- 1999-03-25 DK DK99912026T patent/DK1071702T3/da active
- 1999-03-25 CA CA002325933A patent/CA2325933C/en not_active Expired - Lifetime
- 1999-03-25 UA UA2000095546A patent/UA70318C2/uk unknown
- 1999-03-25 NZ NZ507309A patent/NZ507309A/xx not_active IP Right Cessation
- 1999-03-25 KR KR1020007010903A patent/KR100615560B1/ko not_active Expired - Lifetime
- 1999-03-25 WO PCT/IL1999/000173 patent/WO1999052932A1/en not_active Ceased
- 1999-03-25 AU AU30515/99A patent/AU742944B2/en not_active Expired
- 1999-03-25 JP JP2000543488A patent/JP5031942B2/ja not_active Expired - Lifetime
- 1999-03-25 ES ES99912026T patent/ES2183526T3/es not_active Expired - Lifetime
- 1999-03-25 BR BRPI9909908A patent/BRPI9909908B8/pt not_active IP Right Cessation
- 1999-03-25 CZ CZ20003625A patent/CZ300824B6/cs not_active IP Right Cessation
- 1999-03-25 EA EA200000888A patent/EA003392B1/ru not_active IP Right Cessation
- 1999-03-25 DE DE69902647T patent/DE69902647T2/de not_active Expired - Lifetime
2000
- 2000-09-29 US US09/675,656 patent/US6395722B1/en not_active Expired - Lifetime
- 2000-10-04 NO NO20004998A patent/NO316875B1/no not_active IP Right Cessation
- 2000-10-23 US US09/693,928 patent/US6384024B1/en not_active Expired - Lifetime
2002
- 2002-02-21 US US10/078,671 patent/US6589946B2/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
NO20004998D0 (no)	2000-10-04
EP1071702A1 (en)	2001-01-31
US6589946B2 (en)	2003-07-08
EA200000888A1 (ru)	2001-04-23
ES2183526T3 (es)	2003-03-16
DE69902647T2 (de)	2003-04-24
PL343360A1 (en)	2001-08-13
DE69902647D1 (de)	2002-10-02
BR9909908A (pt)	2000-12-26
DK1071702T3 (da)	2002-12-30
BRPI9909908B8 (pt)	2021-05-25
IL123998A (en)	2004-09-27
PL199271B1 (pl)	2008-09-30
ATE222923T1 (de)	2002-09-15
HU229513B1 (en)	2014-01-28
CN100386339C (zh)	2008-05-07
NO316875B1 (no)	2004-06-07
CN1296492A (zh)	2001-05-23
EA003392B1 (ru)	2003-04-24
JP5031942B2 (ja)	2012-09-26
NZ507309A (en)	2003-06-30
CZ20003625A3 (cs)	2001-01-17
UA70318C2 (uk)	2004-10-15
US6395722B1 (en)	2002-05-28
HUP0101653A2 (hu)	2001-12-28
US20020091111A1 (en)	2002-07-11
ID26042A (id)	2000-11-16
AU3051599A (en)	1999-11-01
KR100615560B1 (ko)	2006-08-25
CA2325933A1 (en)	1999-10-21
TR200002876T2 (tr)	2000-12-21
BR9909908B1 (pt)	2014-03-18
JP2002511482A (ja)	2002-04-16
HUP0101653A3 (en)	2002-02-28
US6384024B1 (en)	2002-05-07
WO1999052932A1 (en)	1999-10-21
AU742944B2 (en)	2002-01-17
SI1071702T1 (en)	2003-04-30
CA2325933C (en)	2008-06-10
EP1071702B1 (en)	2002-08-28
CZ300824B6 (cs)	2009-08-19
PT1071702E (pt)	2003-01-31
KR20010042342A (ko)	2001-05-25

Legal Events

Date	Code	Title	Description
2015-04-20	CHAD	Change of the owner's name or address (par. 44 patent law, par. patentforskriften)	Owner name: GALMED RESEARCH AND DEVELOPMENT LTD, IL
2019-04-08	MK1K	Patent expired

Publication	Publication Date	Title
NO20004998D0 (no)	2000-10-04	Fettsyrederivater av gallesyrer og gallesyrederivater
TR199801195T2 (xx)	1998-10-21	Tedavide yararl� kinolin ve kinozilin bile�ikleri.
JO2503B1 (en)	2009-10-05	Benzathiazole derivatives
EP1244455A4 (en)	2004-11-03	METHOD FOR THE TREATMENT OF VASCULAR DISEASES THAT ARE CHARACTERIZED BY AN INSUFFICIENCY OF NITROGEN MONOXIDE
CA2260777A1 (en)	1998-02-12	Pentafluorobenzenesulfonamides and analogs
NO940789D0 (no)	1994-03-07	Quinolinkarboksylsyrederivater, deres fremstilling og anvendelse
DK0841949T3 (da)	2006-08-21	Anvendelse af saccharid-konjugater
IT1304501B1 (it)	2001-03-19	Uso di derivati di acidi biliari coniugati con complessi metallicicome "blood pool agents" per l'indagine diagnostica tramite risonanza
CA2370244A1 (en)	2000-11-02	Piperidine derivatives
MXPA03009553A (es)	2004-05-24	Uso de acido biliar o conjugados de acidos grasos de sales biliares.
TR199802060T2 (xx)	1999-01-18	Aminoisokinolinler ve aminopiridin t�revlerinin iltihap �nleyiciler olarak kullan�m�.
ATE389655T1 (de)	2008-04-15	Pyrimidinderivate
NO940777D0 (no)	1994-03-04	Anvendelse av et pregnanderivat
MX9707046A (es)	1998-02-28	Composiciones que comprenden nicotinilalanina y un inhibidor de conjugacion de glicina o vitamina b6.
YU19302A (sh)	2004-11-25	4-benzilaminohinolin konjugovan žučnom kiselinom i njegovi heteroanalozi, postupak za njihovu proizvodnju, lekovi koji sadrže ta jedinjenja i njihova primena
CY1105591T1 (el)	2010-07-28	Αναστολεις για συνθαση του 20-ηετε
WO2001030804A3 (en)	2002-01-10	Salt form of a conjugate useful in the treatment of prostate cancer
AP9400608A0 (en)	1995-07-12	"New nicotinic acid derivative".
ATE254460T1 (de)	2003-12-15	Anhydrovinblastin zur behandlung von krebs
CA2215319A1 (en)	1996-09-19	Compositions comprising nicotinylalanine and an inhibitor of glycine conjugation or vitamin b6