Glycan therapeutics and related methods thereof

Abstract

Preparations of glycan therapeutics, pharmaceutical compositions and medical foods thereof, optionally comprising micronutrients, polyphenols, prebiotics, probiotics, or other agents are provided and methods of making same. Also provided are methods of using said glycan therapeutics, e.g. for the modulation of human gastrointestinal microbiota and to treat dysbioses.

We claim: 
     
         1 . A pharmaceutical composition comprising a glycan therapeutic preparation provided as a unit-dosage form formulated for oral or rectal administration to the large intestine or colon, wherein:
 i) the glycan therapeutic preparation comprises branched glycans that comprise glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units,   ii) the average degree of branching (DB) of the branched glycans in the glycan therapeutic preparation is at least 0.01,   iii) at least 50% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units,   iv) the ratio of alpha- to beta-glycosidic bonds present in the glycans of the glycan therapeutic preparation is between about 0.8:1 to about 5:1,   v) at least two of the glycosidic bonds independently comprise a 1->2 glycosidic bond, a 1->3 glycosidic bond, a 1->4 glycosidic bond, or a 1->6 glycosidic bond, and   vi) the glycan therapeutic preparation has a final solubility limit in water of at least about 60 Brix at 23° C.   
     
     
         2 . The pharmaceutical composition of  claim 1 , formulated for oral administration as a liquid. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the unit-dosage form is a beverage, a syrup, an aqueous solution, or an aqueous suspension. 
     
     
         4 . The pharmaceutical composition of  claim 1 , formulated for oral administration as a solid. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the unit-dosage form is a tablet, a pill, a capsule, a lozenge, a candy, or a powder. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the powder is formulated for reconstitution in an aqueous solution prior to oral administration. 
     
     
         7 . The pharmaceutical composition of  claim 1 , formulated for rectal administration as a solid or liquid. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the unit-dosage form is an enema or suppository. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the unit-dosage form is formulated as a delayed release or time controlled system. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the unit-dosage form provides from about 5 grams per day to about 50 grams per day. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the unit-dosage form provides from about 1 gram per day to about 10 grams per day. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the unit-dosage form has a caloric value of about 0.1 kcal to about 10 kcal. 
     
     
         13 . The pharmaceutical composition of  claim 1 , further comprising a pharmaceutically acceptable carrier or excipient. 
     
     
         14 . The pharmaceutical composition of  claim 1 , further comprising second therapeutic agent. 
     
     
         15 . The pharmaceutical composition of  claim 1 , further comprising a polyphenol preparation. 
     
     
         16 . The pharmaceutical composition of  claim 1 , further comprising a preparation of a probiotic microbe. 
     
     
         17 . The pharmaceutical composition of  claim 1 , wherein the average degree of branching (DB) of the branched glycans in the glycan preparation is between 0.01 and 0.5. 
     
     
         18 . The pharmaceutical composition of  claim 1 , wherein at least 75% of the glycans in the glycan therapeutic preparation have an average molecular weight of at least about 400 g/mol and less than 3300 g/mol. 
     
     
         19 . A pharmaceutical kit comprising a plurality of unit dosage forms comprising the pharmaceutical composition comprising a glycan therapeutic preparation of  claim 1  packaged in a single container. 
     
     
         20 . The pharmaceutical kit of  claim 19 , further comprising instructional material. 
     
     
         21 . A pharmaceutical kit comprising:
 a) a unit dosage form comprising:
 i) a first dosage element comprising the pharmaceutical composition comprising a glycan therapeutic preparation of  claim 1 , and 
 ii) a second dosage element comprising a preparation of a probiotic microbe, a preparation of a polyphenol, a dietary component, a second pharmaceutical agent or drug, or a combination thereof, and 
   b) packaging.   
     
     
         22 . The pharmaceutical kit of  claim 21 , wherein the second dosage element is formulated in a modified release form. 
     
     
         23 . A medical food comprising a glycan therapeutic preparation provided as a unit-dosage form formulated for enteral feeding, wherein:
 i) the glycan therapeutic preparation comprises branched glycans that comprise glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units,   ii) the average degree of branching (DB) of the branched glycans in the glycan therapeutic preparation is at least 0.01,   iii) at least 50% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units,   iv) the ratio of alpha- to beta-glycosidic bonds present in the glycans of the glycan therapeutic preparation is between about 0.8:1 to about 5:1,   v) at least two of the glycosidic bonds independently comprise a 1->2 glycosidic bond, a 1->3 glycosidic bond, a 1->4 glycosidic bond, or a 1->6 glycosidic bond, and   vi) the glycan therapeutic preparation has a final solubility limit in water of at least about 60 Brix at 23° C.   
     
     
         24 . The medical food of  claim 23 , formulated for nasal tube administration or oral tube administration. 
     
     
         25 . The medical food of  claim 24 , wherein the nasal tube administration is nasogastric or nasojejunal tube administration. 
     
     
         26 . The medical food of  claim 24 , wherein the oral tube administration is oral gastric or oral jejunal tube administration. 
     
     
         27 . A dietary supplement formulated for oral administration by mouth comprising a glycan preparation, wherein:
 i) the glycan preparation comprises branched glycans that comprise glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units,   ii) the average degree of branching (DB) of the branched glycans in the glycan preparation is at least 0.01,   iii) at least 50% of the glycans in the glycan preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units,   iv) the ratio of alpha- to beta-glycosidic bonds present in the glycans of the glycan preparation is between about 0.8:1 to about 5:1,   v) at least two of the glycosidic bonds independently comprise a 1->2 glycosidic bond, a 1->3 glycosidic bond, a 1->4 glycosidic bond, or a 1->6 glycosidic bond, and   vi) the glycan preparation has a final solubility limit in water of at least about 60 Brix at 23° C.   
     
     
         28 . The dietary supplement of  claim 27 , further comprising one or more of a vitamin, mineral, herb, botanical, amino acid, enzyme, organ tissue, glandular, and metabolite. 
     
     
         29 . The dietary supplement of  claim 27 , provided as a unit-dosage form and labeled a dietary supplement. 
     
     
         30 . The dietary supplement of  claim 27 , wherein the unit-dosage form is a liquid, a powder, a tablet, a capsule, a softgel, a gelcap, or a bar.