Abstract This invention relates to inhibitors for glycoside-hydrolases derived from bacteria of the order Actinomycetales, means for their production comprising cultivation of a microorganism of the order Actinomycetales in appropriate nutrient solutions under conditions most favorable to growth and production of the enzyme inhibitor and recovering, as a new product, glycoside-hydrolase enzyme inhibitors, from the culture as well as the use of said enzyme inhibitors in pharmaceutically acceptable therapeutic compositions in the treatment of conditions indicating obesity, diabetes, pre-diabetes, gastritis, gastric ulcer, hyperlipidemia (atheriosclerosis) and the like. The invention also contemplates the provision of methods of inhibiting the reaction of carbohydrates and glycoside-hydrolase enzymes and particularly carbohydrate-splitting glycoside-hydrolase enzymes of the digestive tract by means of conducting said reaction of said carbohydrates and glycoside-hydrolase enzymes in the presence of a glycoside-hydrolase enzyme inhibitor for said glycosidehydrolase enzyme derived from a strain of microorganism of the order Actinomycetales. The invention further contemplates the provision of methods for the treatment of indications of the group consisting of obesity, hyperlipidemia (atheriosclerosis), diabetes, pre-diabetes, gastritis, gastric ulcer, duodenal ulcer, and caries induced by the action of glycoside-hydrolase enzymes and carbohydrates, the improvement which comprises employing an enzyme inhibitor for glycoside-hydrolase enzymes produced by a strain of microorganism of the order Actinomycetales.
A GLYCOSIDE-HYDROLASE ENZYME INHIBITOR PRODUCED BY A METHOD COMPRISING CULTURING A MICROORGANISM OF THE ORDER ACTINOMYCETALES AT A TEMPERATURE OF 15*-60*C. AND A PH OR 6-8 FOR AN INCUBATION PERIOD OF ABOUT 1-10 DAYS AND EXTRACTING THE ENZYME INHIBITOR FROM THE RESULTANT CULTURE, WHEREIN SAID ENZYME INHIBITOR: A. IS SUBSTANTIALLY HEAT-STABLE AT NEUTRAL PH VALUES; IS STABLE TO ACID AT PH 2; C. IS STABLE TO ALKALI AT PH 12; D, IS SLOWLY DIALYZALE; E. IS NOT INACTIVATED BY TRYPSIN OR PEPSIN; F. DOES NOT INHIBIT TRYPSIN OR PEPSIN; G. IS NOT RECEPTIVE TO PROTEIN DYES; H. IS FREE FROM CHARACTERISTIC UV ADSORPTION UP TO 250 NM; I. IS NOT INHIBITED BY UREA OF B-MERCAPTOETHANOL; J. IS OF MELECULAR WEIGHT ABOUT 500-6000; AND K. YEILDS MONOSACCHARIDE ON HYDROLYTIC SPLITTING.
Claim 2
Dependent Claim
129 words
A GLYCOSIDE-HYDROLASE ENZYME INHIBITOR PRODUCED BY A METHOD COMPRISING CULTURING A MICROORGANISM OF THE ORDER ACTINOMYCETALES AT A TEMPERATURE OF 15*-60*C. AND A PH OR 6-8 FOR AN INCUBATION PERIOD OF ABOUT 1-10 DAYS AND EXTRACTING THE ENZYME INHIBITOR FROM THE RESULTANT CULTURE, WHEREIN SAID ENZYME INHIBITOR: A. IS SUBSTANTIALLY HEAT-STABLE AT NEUTRAL PH VALUES; IS STABLE TO ACID AT PH 2; C. IS STABLE TO ALKALI AT PH 12; D, IS SLOWLY DIALYZALE; E. IS NOT INACTIVATED BY TRYPSIN OR PEPSIN; F. DOES NOT INHIBIT TRYPSIN OR PEPSIN; G. IS NOT RECEPTIVE TO PROTEIN DYES; H. IS FREE FROM CHARACTERISTIC UV ADSORPTION UP TO 250 NM; I. IS NOT INHIBITED BY UREA OF B-MERCAPTOETHANOL; J. IS OF MELECULAR WEIGHT ABOUT 500-6000; AND K. YEILDS MONOSACCHARIDE ON HYDROLYTIC SPLITTING.
Claim 3
Dependent Claim
21 words
A pharmaceutical composition comprising an effective amount of the glycoside-hydrolase enzyme inhibitor of claim 1 in admixture with a pharmaceutically-acceptable diluent.
Claim 4
Dependent Claim
10 words
The pharmaceutical composition of claim 2 in dosage unit form.
Claim 5
Dependent Claim
40 words
In a method for treating diabetes induced by the interaction of carbohydrate-splitting enzymes and carbohydrates in the digestive tract, the improvement which comprises administering to a patient suffering therefrom an effective amount of the glycoside-hydrolase enzyme inhibitor of claim 1.