Compositions and Methods for Managing Weight

Abstract

The present disclosure provides Diels-Alder adducts of chalcone and prenylphenyl moieties capable of modulating the activity of cannabinoid receptors, and to oligomers of flavan-3-ol capable of modulating fat absorption and storage. Such Diels-Alder adducts of chalcone and prenylphenyl moieties or oligomers of flavan-3-ol can optionally be used in combination with other weight management agents, such as anorectic agents, a lipase inhibitors, other cannabinoid receptor modulators, psychotropic agents, insulin sensitizers, stimulants, or satiety agents, as well as to methods of use thereof such as treating or preventing weight gain or obesity, promoting weight loss, appetite suppression, modifying satiety, or the like.

We claim: 
     
         1 . A composition, comprising a mixture of a  Morus  extract enriched for one or more Diels-Alder adducts of a chalcone and a prenylphenyl moiety, a  Magnolia  extract, and a Yerba Mate extract. 
     
     
         2 . The composition according to  claim 1 , wherein the  Morus  extract is from  Morus alba , the  Magnolia  extract is from  Magnolia officinalis , and the Yerba Mate extract is from  Ilex paraguayensis.    
     
     
         3 . The composition according to  claim 1 , wherein the one or more Diels-Alder adducts of a chalcone and a prenylphenyl moiety are compounds having a structure of Formula Ib or IIb: 
       
         
           
           
               
               
           
         
         or a pharmaceutically or nutraceutically acceptable salt, tautomer, glycoside, prodrug or stereoisomer thereof, wherein: 
         R 4a , R 5a , R 6a  and R 7a  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 4a , R 1a , R 6a  or R 7a  joins with another of R 4a , R 5a , R 6a  or R 7a  to form a heterocyclic or heteroaromatic; 
         R 4b , R 5b , R 6b  and R 7b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 4b , R 5b , R 6b , R 7b  joins with another of R 4b , R 5 , R 6b , R 7b  to form a heterocyclic or heteroaromatic ring; 
         R 8a , R 8b , R 9a , R 9b , R 10a , R 10b , R 11a  and R 11b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 8a , R 9a , R 10a  or R 11a  or one of R 8b , R 9b , R 10b  or R 11b  joins with another of R 8a , R 9a , R 10a  or R 11a  or another one of R 8b , R 9b , R 10b  or R 11b  respectively, to form a heterocyclic or heteroaromatic ring; 
         R 12a , R 13a , R 14a  and R 15a  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 12a , R 13a , R 14a , R 15a  joins with another of R 12a , R 13a , R 14a  or R 15a  to form a heterocyclic or heteroaromatic ring; and 
         R 12b , R 13b , R 14b  and R 15b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 2b , R 13b , R 14b , R 15b b joins with another of R 2b , R 13b , R 14b  or R 15b  to form a heterocyclic or heteroaromatic ring. 
       
     
     
         4 . The composition of  claim 1 , wherein at least two of R 4a , R 4b , R 5a , R 5b , R 6a , R 6b , R 7a , R 7b , R 8a , R 8b , R 9a , R 9b , R 10a , R 10b , R 11a , R 11b , R 12a , R 12b , R 13a , R 13b , R 14a , R 14b , R 15a  and R 15b  are hydroxyl. 
     
     
         5 . The composition according to  claim 1 , wherein the  Morus  extract is enriched for Albanin G, Kuwanon G, Morusin, or any combination thereof. 
     
     
         6 . The composition according to  claim 1 , wherein the  Magnolia  extract is enriched for magnolol, honokiol, or both. 
     
     
         7 . The composition according to  claim 1 , wherein the Yerba Mate extract is enriched for caffeine, dicaffeoylquinic acid, or both. 
     
     
         8 . The composition according to  claim 1 , wherein the composition further comprises a pharmaceutically or nutraceutically acceptable carrier, diluent, or excipient, wherein the pharmaceutical or nutraceutical formulation comprises from about 0.5 weight percent (wt %) to about 90 wt % of active ingredients of the extract mixture. 
     
     
         9 . The composition according to  claim 8 , wherein the composition is formulated as a tablet, capsule, powder, or granule. 
     
     
         10 . A composition, comprising a mixture of a  Morus  extract enriched for Diels-Alder adducts of a chalcone and a prenylphenyl moiety, a  Magnolia  extract, and a Mutamba extract. 
     
     
         11 . The composition according to  claim 10 , wherein the  Morus  extract is from  Morus alba , the  Magnolia  extract is from  Magnolia officinalis , and the Mutamba extract is from  Guazuma ulmifolia.    
     
     
         12 . The composition according to  claim 10 , wherein the one or more Diels-Alder adducts of a chalcone and a prenylphenyl moiety are compounds having a structure of Formula Ib or IIb: 
       
         
           
           
               
               
           
         
         or a pharmaceutically or nutraceutically acceptable salt, tautomer, glycoside, prodrug or stereoisomer thereof, wherein: 
         R 4a , R 5a , R 6a  and R 7a  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 4a , R 5a , R 6a  or R 7a  joins with another of R 4a , R 5a , R 6a  or R 7a  to form a heterocyclic or heteroaromatic; 
         R 4b , R 5b , R 6b  and R 7b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 4b , R 5b , R 6b , R 7b  joins with another of R 4b , R 5 , R 6b , R 7b  to form a heterocyclic or heteroaromatic ring; 
         R 8a , R 5b , R 9a , R 9b , R 10a , R 10b , R 11a  and R 11b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 5a , R 9a , R 10a  or R 11a  or one of R 8b , R 9b , R 10b  or R 11b  joins with another of R 5a , R 9a , R 10a  or R 11a  or another one of R 8b , R 9b , R 10b  or R 11b  respectively, to form a heterocyclic or heteroaromatic ring; 
         R 12a , R 13a , R 14a  and R 15a  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 12a , R 13a , R 14a , R 15a  joins with another of R 12a , R 13a , R 14a  or R 15a  to form a heterocyclic or heteroaromatic ring; and 
         R 12b , R 13b , R 14b  and R 15b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 12b , R 13b , R 14b , R 15b  joins with another of R 12b , R 13b , R 14b , or R 15b  to form a heterocyclic or heteroaromatic ring. 
       
     
     
         13 . The composition of  claim 10 , wherein at least two of R 4a , R 4b , R 5a , R 5b , R 6a , R 6b , R 7a , R 7b , R 8a , R 8b , R 9a , R 9b , R 10a , R 10b , R 11a , R 11b , R 12a , R 12b , R 13a , R 13b , R 14a , R 14b , R 15a  and R 15b  are hydroxyl. 
     
     
         14 . The composition according to  claim 10 , wherein the  Morus  extract is enriched for Albanin G, Kuwanon G, Morusin, or any combination thereof. 
     
     
         15 . The composition according to  claim 10 , wherein the  Magnolia  extract is enriched for magnolol, honokiol, or both. 
     
     
         16 . The composition according to  claim 10 , wherein the Mutamba extract comprises one or more oligomers comprising from two to thirty subunits, wherein the subunits have, at each occurrence, independently the following structure (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof, wherein:
 R 1a  and R 1b  are, at each occurrence, independently H, hydroxyl, halo, a gallic acid ester, a glycoside, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl, or a direct bond to an adjacent subunit; 
 R 2  is, at each occurrence, independently H or an ether bond to an adjacent subunit; 
 R 3  is, at each occurrence, independently H or a direct bond to an adjacent subunit; 
 R 4  is, at each occurrence, OH or an ether bond to an adjacent subunit; and 
 R 5a , R 5b , R 5c , R 5d  and R 5e  are, at each occurrence, independently H, hydroxyl, halo, a gallic acid ester, a glycoside, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl or aralkylcarbonyl, 
 wherein at least one of R 1a , R 1b , R 2 , R 3  or R 4  is a direct bond or ether bond to an adjacent subunit. 
 
     
     
         17 . The composition according to  claim 10 , wherein the Mutamba extract is enriched for procyanidins, procyanidin dimers, procyanidin trimers, procyanidin tetramers, procyanidin pentamers, procyanidin hexamers, condensed tannins, oligomers of catechin or epicatechin, epicatechin, or any combination thereof. 
     
     
         18 . The composition according to  claim 10 , wherein the composition further comprises a pharmaceutically or nutraceutically acceptable carrier, diluent, or excipient, wherein the pharmaceutical or nutraceutical formulation comprises from about 0.5 weight percent (wt %) to about 90 wt % of active ingredients of the extract mixture. 
     
     
         19 . The composition according to  claim 18 , wherein the composition is formulated as a tablet, capsule, powder, or granule. 
     
     
         20 . A composition, comprising a mixture of a  Morus  extract enriched for Diels-Alder adducts of a chalcone and a prenylphenyl moiety, a Rosemary extract, and a Yerba Mate extract. 
     
     
         21 . The composition according to  claim 20 , wherein the  Morus  extract is from  Morus alba , the Rosemary extract is from  Rosmarinus officinalis , and the Yerba Mate extract is from  Ilex paraguayensis.    
     
     
         22 . The composition according to  claim 20 , wherein the one or more Diels-Alder adducts of a chalcone and a prenylphenyl moiety are compounds having a structure of Formula Ib or IIb: 
       
         
           
           
               
               
           
         
         or a pharmaceutically or nutraceutically acceptable salt, tautomer, glycoside, prodrug or stereoisomer thereof, wherein: 
         R 4a , R 5a , R 6a  and R 7a  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 4a , R 1a , R 6a  or R 7a  joins with another of R 4a , R 5a , R 6a  or R 7a  to form a heterocyclic or heteroaromatic; 
         R 4b , R 5b , R 6b  and R 7b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 4b , R 5b , R 6b , R 7b  joins with another of R 4b , R 5b , R 6b , R 7b  to form a heterocyclic or heteroaromatic ring; 
         R 8a , R 8b , R 9a , R 9b , R 10a , R 10b , R 11a  and R 11b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 8a , R 9a , R 10a  or R 11a  or one of R 8b , R 9b , R 10b  or R 11b  joins with another of R 8a , R 9a , R 10a  or R 11a  or another one of R 8b , R 9b , R 10b  or R 11b , respectively, to form a heterocyclic or heteroaromatic ring; 
         R 12a , R 13a , R 14a  and R 15a  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 12a , R 13a , R 14a , R 15a  joins with another of R 12a , R 13a , R 14a  or R 15a  to form a heterocyclic or heteroaromatic ring; and 
         R 12b , R 13b , R 14b  and R 15b  are each independently H, hydroxyl, halogen, sulfhydryl, amino, aldehyde, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkthio, C 1-12  alkyamino, aryl, heteroaryl, aralkyl, alkyl carbonyl, aralkylcarbonyl or one of R 12b , R 13b , R 14b , R 15b  joins with another of R 2b , R 13b , R 14b , or R 15b  to form a heterocyclic or heteroaromatic ring. 
       
     
     
         23 . The composition of  claim 20 , wherein at least two of R 4a , R 4b , R 5a , R 5b , R 6a , R 6b , R 7a , R 7b , R 8a , R 8b , R 9a , R 9b , R 10a , R 10b , R 11a , R 11b , R 12a , R 12b , R 13a , R 13b , R 14a , R 14b , R 15a  and R 15b  are hydroxyl. 
     
     
         24 . The composition according to  claim 20 , wherein the  Morus  extract is enriched for Albanin G, Kuwanon G, Morusin, or any combination thereof. 
     
     
         25 . The composition according to  claim 20 , wherein the Rosemary extract is enriched for carnosol, carnosoic acid, ursolic acid, or any combination thereof. 
     
     
         26 . The composition according to  claim 20 , wherein the Yerba Mate extract is enriched for caffeine, dicaffeoylquinic acid, or both. 
     
     
         27 . The composition according to  claim 20 , wherein the composition further comprises a pharmaceutically or nutraceutically acceptable carrier, diluent, or excipient, wherein the pharmaceutical or nutraceutical formulation comprises from about 0.5 weight percent (wt %) to about 90 wt % of active ingredients of the extract mixture. 
     
     
         28 . The composition according to  claim 27 , wherein the composition is formulated as a tablet, capsule, powder, or granule. 
     
     
         29 . A method for maintaining body weight in a mammal comprising administering an effective amount of a composition according to  claim 1 . 
     
     
         30 . A method for promoting a healthy lipid profile by lowering LDL cholesterol, lowering total cholesterol, lowering triglyceride, or increasing HDL in a mammal comprising administering an effective amount of a composition according to  claim 10 . 
     
     
         31 . A method for treating, preventing, or managing weight gain in a mammal comprising administering an effective amount of a composition according to  claim 20 .