US 3856953 A
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:
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Description (OCR text may contain errors)
nited States Patent [191 Saltzman Dec. 24, T974 METHOD OF TREATING IFATTY LIVER  Inventor: William H. Saltzman, New
 Assignee: llntellectual Property Development Corporation, New Rochelle, N.Y.
 Filed: May 15, 1973  Appl. No.: 360,572
 US. Cl 424/238, 424/242, 424/243  lint. Cl A61k 17/00  Field of Search 424/238  References Cited UNITED STATES PATENTS 3,180,794 4/1965 Antonides 424/238 Primary Examiner-Henry A. French  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:
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.