Theobromine compositions useful for increasing fetal weight gain and enhancing bone properties

Abstract

Compositions and methods for culturing cells with theobromine are provided, as well as cells derived thereby. Theobromine compositions for enhancing bone formation, increasing bone density, increasing interconnections of internal bone, increasing bone mass, treating cartilage and/or bone defects, increasing fetal birth weight, preventing tooth decay, remineralizing a tooth surface, treating dentine hypersensitivity, and application to a bone site to promote new bone growth at the site are also provided.

What is claimed is: 
     
         1 . An isolated cell in a culture medium, said culture medium comprising theobromine, a salt or double salt of theobromine, or a co-crystal comprising theobromine. 
     
     
         2 . The isolated cell of  claim 1 , wherein said isolated cell is a mammalian cell. 
     
     
         3 . The isolated cell of  claim 1 , wherein said isolated cell is a stem cell. 
     
     
         4 . The stem cell of  claim 3 , wherein said stem cell is a mesenchymal stem cell. 
     
     
         5 . The cell of  claim 1 , wherein said theobromine, salt or double salt of theobromine, or co-crystal comprising theobromine is from 1 to 300 μM. 
     
     
         6 . A method of culturing a cell, the method comprising:
 culturing said cell in a culture medium, wherein said culture medium comprises theobromine, a salt or double salt of theobromine, or a co-crystal comprising theobromine.   
     
     
         7 . The method of  claim 6 , wherein said cell is a mammalian cell. 
     
     
         8 . The method of  claim 6 , wherein said cell is a stem cell. 
     
     
         9 . The method of  claim 8 , wherein said stem cell is a mesenchymal stem cell. 
     
     
         10 . The method of  claim 6 , wherein said theobromine is from 1 to 300 μM. 
     
     
         11 . A culture medium comprising theobromine, a salt or double salt of theobromine, or a co-crystal comprising theobromine. 
     
     
         12 . The culture medium of  claim 11 , wherein said theobromine, salt or double salt of theobromine, or co-crystal comprising theobromine is from 1 to 300 μM. 
     
     
         13 . The culture medium of  claim 11 , wherein said theobromine, salt or double salt of theobromine, or co-crystal comprising theobromine is from 1 to 100 μM. 
     
     
         14 . A composition comprising:
 a) demineralized osteogenic bone powder with a particle size of about 250 pun to about 5 mm; and   b) theobromine, a salt or double salt of theobromine, or a co-crystal comprising theobromine, a salt, or double salt of theobromine.   
     
     
         15 . A nutritional formulation comprising theobromine, a salt or double salt of theobromine, or a co-crystal comprising theobromine, a salt or double salt of theobromine, said nutritional formulation selected from the group consisting of: baked goods; baking mixes; chewing gum; breakfast cereals; cheese products; nuts and nut products; gelatins, pudding, custard, and fillings; frozen dairy products; milk products; meal-replacement beverages; yogurt; yogurt drinks; dairy product analogs; hard candy; soft candy; soups; soup mixes; snack foods; beverages; processed fruit juice; fruit smoothies; powdered fruit-flavored drinks; processed vegetable juice; sports or isotonic drinks; meal-replacement beverages; non-milk-based beverages; soy milk; bottled water; coffee; tea; fats and oils; fish products; plant protein products; poultry products; meat products. 
     
     
         16 . The nutritional formulation of  claim 15 , wherein said theobromine, a salt or double salt of theobromine, or a co-crystal comprising theobromine, a salt or double salt of theobromine is provided at a concentration of from 5 mg/serving to 130 mg/serving. 
     
     
         17 . A method of treating osteoporosis, enhancing bone formation, increasing bone density, increasing interconnections of internal bone, increasing bone mass, treating cartilage and/or bone defects, increasing fetal birth weight, or combinations thereof, in a subject in need thereof, the method comprising providing to said subject, for consumption, the nutritional formulation of  claim 16 . 
     
     
         18 . A method of preventing tooth decay, remineralizing a tooth surface, treating dentine hypersensitivity, or combinations thereof, in a subject in need thereof, the method comprising providing to said subject, for consumption, the nutritional formulation of  claim 16 . 
     
     
         19 . A method of improving maternal or child health during the stages of preconception, pregnancy, lactation, and/or postpartum, the method comprising providing the nutritional formulation of  claim 16  to a woman in need thereof, for consumption, prior to conception, during a pregnancy, postpartum, or combinations thereof. 
     
     
         20 . The method of  claim 19 , wherein said improving maternal or child health comprises increasing fetal weight gain, enhancing fetal or maternal bone formation, increasing fetal or maternal bone density, increasing interconnections of internal fetal or maternal bone, increasing fetal or maternal bone mass, treating maternal osteoporosis, and combinations thereof.