US3856953A - Method of treating fatty liver - Google Patents
Method of treating fatty liver Download PDFInfo
- Publication number
- US3856953A US3856953A US00360572A US36057273A US3856953A US 3856953 A US3856953 A US 3856953A US 00360572 A US00360572 A US 00360572A US 36057273 A US36057273 A US 36057273A US 3856953 A US3856953 A US 3856953A
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- liver
- fatty liver
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- 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
-
- 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
Definitions
- ABSTRACT This invention relates to a method for treating mammals suffering from fatty infiltration of the liver, which comprises administering to a mammal suffering from a fatty liver, a small but effective amount of a compound of the formula:
- This invention relates to a method of therapeutically treating mammals suffering from fatty infiltration of the liver.
- This condition of the liver is usually described as Fatty Liver, and is characterized by an excessive deposition of fat in the liver and its cells.
- This condition is usually seen in patients suffering from such conditions as chronic alcoholism, alcoholic cirrhosis, exogenous obesity, metabolic disorders, such as diabetes mellitus, and other like diseases where fatty liver is a histologic abnormality.
- the patient usually presents an enlarged palpable tender liver; elevated liver function test values; and a large amount of fat infiltration on examination of a biopsy of the liver.
- each Y is hydroxy, acyloxy, or alkoxy
- each X is hydrogen; each Y is hydroxy and R is hydroxy.
- the compounds employed in the practice of this invention may be administered in the form of their nontoxic pharmaceutically acceptable salts, for example, the alkaline metal salts. such as the sodium or potassium salts.
- the preferred acyloxy radicals are those of hydrocarbon carboxylic acids of less than 12 carbon atoms, as exemplified by the lower alkanoic acids, the lower alkenoic acids, the monocyclic aryl carboxylic acids, the monocyclic aryl carboxylic acids, the monocyclic aryl lower alkanoic acids, the cycloalkane carboxylic acids and the cycloalkene carboxylic acids.
- the compounds which may be employed in the practice of this invention may be included such compounds as, 301,704,]Za-trihydroxy-SB-cholanic acid; 3a,7a-dihydroxy-lZaacyloxy-SB-cholanic acid; 3a,7a,lZatriacyloxy-SB-cholanic acid; 3a-hydroxy- 7a,]2a-diacyloxy-5B-cholanic acid; 3a,7a-dihydroxyl2a-alkoxy-5B-cholanic acid; 3a-hydroxy-7a, 1 2adiacyloxy-SB-cholanic acid, and other like compounds. Most preferably, it is desired to utilize the compound,
- the compounds of this invention may be administered to the patients being treated in accordance with the method of this i'hvention.
- the compositions of this invention are orally administered to the patient in a daily amount of from about mg. to about 1,500 mg. The best results appear to be obtained when the dosage is in the range of from about 0.5 to about 1.5 gm. per day. More specifically, it has been found that very satisfactory results are obtained when up to about 750 mg. per day of the compound are administered to the patient being treated; the optimum daily dosage appearing to be about 500 to 750 mg. per day, although other dosage levels have been found to give beneficial results also. It has been found that the daily administration of more than 1.5 gm. of the respective active substance of this invention imparts no additional beneficial effect to the patient beyond that achieved with a lesser daily dosage level.
- the compounds hereof may be incorporated in such suitable final dosage forms as may be satisfactorily prepared and employed by the worker skilled in the art.
- the commonly employed pharmaceutically acceptable dosage forms suitable for oral administration containing the compounds hereof in sufficient concentration to attain the desired results may be utilized.
- the pharmaceutically acceptable, non-toxic inert carriers usually employed for such purposes may be utilized to prepare such dosage forms as tablets, capsules, elixirs, solutions, suspensions and the like. Most preferably, satisfactory results have been obtained by the use of tablets or capsules containing the active ingredient in a concentration of from about 50 to about 500 mg., although other concentrations have also provided a satisfactory result.
- acyloxy moiety is from a hydrocarbon carboxylic acid of less than 12 carbon atoms.
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
This invention relates to a method for treating mammals suffering from fatty infiltration of the liver, which comprises administering to a mammal suffering from a fatty liver, a small but effective amount of a compound of the formula:
WHEREIN EACH X is hydrogen; EACH Y is hydroxy, acyloxy, or alkoxy; X and Y when taken together is oxo (O ); R is hydroxy, alkoxy, NHCH2COOH, or NHCH2CH2SO3H; and the nontoxic, pharmaceutically acceptable salts thereof.
WHEREIN EACH X is hydrogen; EACH Y is hydroxy, acyloxy, or alkoxy; X and Y when taken together is oxo (O ); R is hydroxy, alkoxy, NHCH2COOH, or NHCH2CH2SO3H; and the nontoxic, pharmaceutically acceptable salts thereof.
Description
nited States Patent [191 Saltzman Dec. 24, T974 METHOD OF TREATING IFATTY LIVER [75] Inventor: William H. Saltzman, New
Rochelle, N.Y.
[73] Assignee: llntellectual Property Development Corporation, New Rochelle, N.Y.
[22] Filed: May 15, 1973 [21] Appl. No.: 360,572
[52] US. Cl 424/238, 424/242, 424/243 [51] lint. Cl A61k 17/00 [58] Field of Search 424/238 [56] References Cited UNITED STATES PATENTS 3,180,794 4/1965 Antonides 424/238 Primary Examiner-Henry A. French [57] ABSTRACT This invention relates to a method for treating mammals suffering from fatty infiltration of the liver, which comprises administering to a mammal suffering from a fatty liver, a small but effective amount of a compound of the formula:
COR
3 Claims, N0 Drawings METHOD OF TREATING FATTY LIVER This invention relates to a method of therapeutically treating mammals suffering from fatty infiltration of the liver. This condition of the liver is usually described as Fatty Liver, and is characterized by an excessive deposition of fat in the liver and its cells. This condition is usually seen in patients suffering from such conditions as chronic alcoholism, alcoholic cirrhosis, exogenous obesity, metabolic disorders, such as diabetes mellitus, and other like diseases where fatty liver is a histologic abnormality. In these cases, the patient usually presents an enlarged palpable tender liver; elevated liver function test values; and a large amount of fat infiltration on examination of a biopsy of the liver.
1 have now found a method whereby these patients suffering from fatty liver may be successfully therapeutically treated. I have discovered a method whereby the fatty liver is defatted and liver function is restored to normal. I have discovered a method of defatting fatty liver in vivo, which comprises administering to a patient with a fatty liver, a small but effective amount of a compound of the formula:
i lbort each X is hydrogen;
each Y is hydroxy, acyloxy, or alkoxy;
X and Y, when together, is x0 (0 R is hydroxy, alkoxy, NHCH COOH NHCH CH SO H; and the non-toxic, pharmaceutically acceptable salts thereof.
In the most preferred embodiment of this invention, each X is hydrogen; each Y is hydroxy and R is hydroxy.
The compounds employed in the practice of this invention may be administered in the form of their nontoxic pharmaceutically acceptable salts, for example, the alkaline metal salts. such as the sodium or potassium salts.
The preferred acyloxy radicals are those of hydrocarbon carboxylic acids of less than 12 carbon atoms, as exemplified by the lower alkanoic acids, the lower alkenoic acids, the monocyclic aryl carboxylic acids, the monocyclic aryl carboxylic acids, the monocyclic aryl lower alkanoic acids, the cycloalkane carboxylic acids and the cycloalkene carboxylic acids.
Among the compounds which may be employed in the practice of this invention may be included such compounds as, 301,704,]Za-trihydroxy-SB-cholanic acid; 3a,7a-dihydroxy-lZaacyloxy-SB-cholanic acid; 3a,7a,lZatriacyloxy-SB-cholanic acid; 3a-hydroxy- 7a,]2a-diacyloxy-5B-cholanic acid; 3a,7a-dihydroxyl2a-alkoxy-5B-cholanic acid; 3a-hydroxy-7a, 1 2adiacyloxy-SB-cholanic acid, and other like compounds. Most preferably, it is desired to utilize the compound,
3a, 7a,]2a-trihydroxy-SB-cholanic acid in the practice of this invention.
The compounds of this invention may be administered to the patients being treated in accordance with the method of this i'hvention. [t has been found that satisfactory results are obtained when the compositions of this invention are orally administered to the patient in a daily amount of from about mg. to about 1,500 mg. The best results appear to be obtained when the dosage is in the range of from about 0.5 to about 1.5 gm. per day. More specifically, it has been found that very satisfactory results are obtained when up to about 750 mg. per day of the compound are administered to the patient being treated; the optimum daily dosage appearing to be about 500 to 750 mg. per day, although other dosage levels have been found to give beneficial results also. It has been found that the daily administration of more than 1.5 gm. of the respective active substance of this invention imparts no additional beneficial effect to the patient beyond that achieved with a lesser daily dosage level.
To achieve the purpose and objectives of this invention, the compounds hereof may be incorporated in such suitable final dosage forms as may be satisfactorily prepared and employed by the worker skilled in the art. Thus, the commonly employed pharmaceutically acceptable dosage forms suitable for oral administration containing the compounds hereof in sufficient concentration to attain the desired results may be utilized. The pharmaceutically acceptable, non-toxic inert carriers usually employed for such purposes may be utilized to prepare such dosage forms as tablets, capsules, elixirs, solutions, suspensions and the like. Most preferably, satisfactory results have been obtained by the use of tablets or capsules containing the active ingredient in a concentration of from about 50 to about 500 mg., although other concentrations have also provided a satisfactory result.
The invention may be further illustrated by the following examples:
EXAMPLE I Final orally administerable dosage forms incorporating the amounts of the active substances set forth in Table A were prepared:
EXAMPLE II J. S., a 57-year old male, suffering from chronic alcoholism, presented a large palpable and tender liver, and upon biopsy, a large amount of fat was found to have infiltrated the liver, confirming the fatty liver diagnosis. The patient was treated with 3st, -7a,l2a-trihydroxy- SB-cholanic acid, administered perorally, t.i.d., in capsules each containing 250 mg. of the compound. After a period of 5 weeks of treatment, the patients liver was rebiopsied and was found to be normal, the fat having disappeared. Liver function tests were also normal.
The invention may be variously otherwise embodied within the scope of the appended claims.
What is claimed is:
pharmaceutically acceptable salts thereof; wherein the acyloxy moiety is from a hydrocarbon carboxylic acid of less than 12 carbon atoms.
2. The method of claim 1, wherein the compound is 5 3a,7a,l2a-trihydroxy-SB-cholanic acid.
3. The method of claim 1, wherein the compound is administered to the patient being treated in a daily dosage amount of from 50 to 1,500 milligrams.
Claims (3)
1. A METHOD FOR THERAPEUTIC TREATMENT OF A PATIENT WITH FATTY LIVER, WHICH COMPRISES; A ORALLY ADMINISTERING TO A PATIENT SUFFERING FROM A FATTY LIVER; B. A SMALL BUT EFFECTIVE AMOUNT OF A COMPOUND SELECTED FROM THE GROUP CONSISTING OF, 3A, 7A, 12A-TRIHYDROXY-5BCHOLANIC ACID; 3A, 7A, 12A-TRIACYLOXY-5B-CHOLANIC ACID; AND THE ACID; 3A, 7A, 12A-DIACYLOXY-5B-CHOLANIC ACID; AND THE HYDROXY -7A, 12A-DIACYLOXY-5B-CHOLANIC ACID; AND THE NON-TOXIC, PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF; WHEREIN THE ACYLOXY MOIETY IS FROM A HYDROCARBON CARBOXYLIC ACID OF LESS THAN 12 CARBON ATOMS.
2. The method of claim 1, wherein the compound is 3 Alpha ,7 Alpha ,12 Alpha -trihydroxy-5 Beta -cholanic acid.
3. The method of claim 1, wherein the compound is administered to the patient being treated in a daily dosage amount of from 50 to 1,500 milligrams.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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US00360572A US3856953A (en) | 1973-05-15 | 1973-05-15 | Method of treating fatty liver |
Applications Claiming Priority (1)
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US00360572A US3856953A (en) | 1973-05-15 | 1973-05-15 | Method of treating fatty liver |
Publications (1)
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US3856953A true US3856953A (en) | 1974-12-24 |
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US00360572A Expired - Lifetime US3856953A (en) | 1973-05-15 | 1973-05-15 | Method of treating fatty liver |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3931403A (en) * | 1973-05-25 | 1976-01-06 | Intellectual Property Development Corporation | Antimicrobial compositions |
EP0113998A2 (en) * | 1982-12-22 | 1984-07-25 | Herpes Pharmaceutical, Inc. | Composition and treatment for herpes simplex viral infections |
EP0186023A2 (en) * | 1984-12-21 | 1986-07-02 | Lehner A.G. | Biliary acid derivatives, process for their preparation and pharmaceutical compositions containing them |
US5122520A (en) * | 1988-04-30 | 1992-06-16 | Sandoz Ltd. | Acid addition salts of amidated taurine or glycine, their preparation and use |
WO1999052932A1 (en) * | 1998-04-08 | 1999-10-21 | Galmed International Ltd. | Fatty acid derivatives of bile acids and bile acid derivatives |
WO2002083147A1 (en) * | 2001-04-17 | 2002-10-24 | Galmed International Limited | Use of bile acid or bile salt fatty acid conjugates |
WO2007016390A1 (en) * | 2005-07-28 | 2007-02-08 | Children's Medical Center Corporation | Matrix metalloproteinase inhibitors for treating fatty liver disease |
US8975246B2 (en) | 2001-04-17 | 2015-03-10 | Galmed Research And Development Ltd. | Bile acid or bile salt fatty acid conjugates |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3180794A (en) * | 1960-09-26 | 1965-04-27 | Armour Pharma | Conjugated bile acid separation |
-
1973
- 1973-05-15 US US00360572A patent/US3856953A/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3180794A (en) * | 1960-09-26 | 1965-04-27 | Armour Pharma | Conjugated bile acid separation |
Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3931403A (en) * | 1973-05-25 | 1976-01-06 | Intellectual Property Development Corporation | Antimicrobial compositions |
EP0113998A2 (en) * | 1982-12-22 | 1984-07-25 | Herpes Pharmaceutical, Inc. | Composition and treatment for herpes simplex viral infections |
EP0113998A3 (en) * | 1982-12-22 | 1984-08-22 | Herpes Pharmaceutical, Inc. | Composition and treatment for herpes simplex viral infections |
EP0186023A2 (en) * | 1984-12-21 | 1986-07-02 | Lehner A.G. | Biliary acid derivatives, process for their preparation and pharmaceutical compositions containing them |
EP0186023A3 (en) * | 1984-12-21 | 1986-10-22 | Lehner A.G. | Biliary acid derivatives, process for their preparation and pharmaceutical compositions containing them |
US5122520A (en) * | 1988-04-30 | 1992-06-16 | Sandoz Ltd. | Acid addition salts of amidated taurine or glycine, their preparation and use |
WO1999052932A1 (en) * | 1998-04-08 | 1999-10-21 | Galmed International Ltd. | Fatty acid derivatives of bile acids and bile acid derivatives |
CZ300824B6 (en) * | 1998-04-08 | 2009-08-19 | Galmed International Limited | Bile acid or bile salt fatty acid conjugates and pharmaceutical composition in which the conjugates are comprised |
EA003392B1 (en) * | 1998-04-08 | 2003-04-24 | Галмед Интернэшнл Лимитид | Bile acid derivatives |
CN100386339C (en) * | 1998-04-08 | 2008-05-07 | 盖尔梅德国际有限公司 | Fatty acid derivatives of bile acids and bile acid derivatives |
EP1790346A3 (en) * | 2001-04-17 | 2007-08-22 | Galmed International Ltd. | Use of bile acid or bile salt fatty acid conjugates |
CZ300489B6 (en) * | 2001-04-17 | 2009-06-03 | Galmed International Limited | Pharmaceutical composition comprising conjugate of bile acid or a salt of bile acid with fatty acid for treatment of fatty liver syndrome |
EA007565B1 (en) * | 2001-04-17 | 2006-12-29 | Галмед Интернэшнл Лимитид | Use of bile acid or bile salt fatty acid compounds for the treatment of fatty lever infiltration |
US20040121993A1 (en) * | 2001-04-17 | 2004-06-24 | Tuvia Gilat | Use of bile acid or bile salt fatty acid conjugates |
AU2007200191B2 (en) * | 2001-04-17 | 2008-09-04 | Galmed Research And Development Ltd. | Use of bile acid or bile salt fatty acid conjugates |
KR100883080B1 (en) | 2001-04-17 | 2009-02-10 | 갈메드 인터내쇼날 리미티드 | Use of bile acid or bile salt fatty acid conjugates |
US7501403B2 (en) | 2001-04-17 | 2009-03-10 | Galmed International Limited | Bile acid or bile salt fatty acid conjugates |
CZ309042B6 (en) * | 2001-04-17 | 2021-12-22 | Galmed Research And Development Ltd. | Use of a bile acid conjugate or bile acid salt with a fatty acid or a pharmaceutical composition containing it for lowering cholesterol and treating hyperglycemia and diabetes |
US20090149537A1 (en) * | 2001-04-17 | 2009-06-11 | Galmed International Limited | Use of Bile Acid or Bile Salt Fatty Acid Conjugates |
WO2002083147A1 (en) * | 2001-04-17 | 2002-10-24 | Galmed International Limited | Use of bile acid or bile salt fatty acid conjugates |
US8975246B2 (en) | 2001-04-17 | 2015-03-10 | Galmed Research And Development Ltd. | Bile acid or bile salt fatty acid conjugates |
US8110564B2 (en) | 2001-04-17 | 2012-02-07 | Galmed International Limited | Bile acid or bile salt fatty acid conjugates |
US7897591B2 (en) | 2005-07-28 | 2011-03-01 | Children's Medical Center Corporation | Method of treating fatty liver disease |
US20090221533A1 (en) * | 2005-07-28 | 2009-09-03 | Children's Medical Center Corporation | Method of treating fatty liver disease |
WO2007016390A1 (en) * | 2005-07-28 | 2007-02-08 | Children's Medical Center Corporation | Matrix metalloproteinase inhibitors for treating fatty liver disease |
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