Synergistic glycocalyx treatment compositions and methods

Abstract

Compositions and methods for treating endothelial glycocalyx include glucosamine, hyaluronan and/or fucoidan, and one or more antioxidants, such as superoxide dismutase, catalase, and/or polyphenol. The compositions improve vascular health by exhibiting beneficial synergistic effects on endothelial glycocalyx over the benefits of taking any single component alone or the sum of reported effects of the individual components. Specifically, components of the composition (1) enhance synthesis of new glycocalyx by (a) providing and (b) increasing production of glycocalyx precursors, (2) protecting existing glycocalyx against damage, such as by oxidation degradation, by (a) providing and (b) increasing production of antioxidants, some of which associate with endothelial glycocalyx, and (3) enhance repair of damaged glycocalyx by (a) providing glycocalyx mimetics and (b) increasing the prevalence of glycocalyx scaffold for association and incorporation thereof.

What is claimed is: 
     
         1 . A composition, comprising:
 one or more molecular precursor of endothelial glycocalyx in an amount of effective to increase production of endothelial glycocalyx in a mammal to which the composition is administered, the one or more molecular precursor of endothelial glycocalyx comprising glucosamine, or a suitable salt or derivative thereof;   one or more antioxidant that associates with endothelial glycocalyx in an amount of effective to at least partially protect existing endothelial glycocalyx against damage caused by enzyme and/or oxidant in a mammal to which the composition is administered, the one or more antioxidant that associates with endothelial glycocalyx comprising superoxide dismutase, or a suitable transition metal conjugate or derivative thereof; and   one or more glycocalyx mimetic in an amount of effective to increase the density of endothelial glycocalyx at a site of endothelial glycocalyx damage in a mammal to which the composition is administered, the one or more glycocalyx mimetic selected from the group consisting of:
 a nonsulfated glycosaminoglycan; 
 hyaluronan, or a suitable salt or derivative thereof; 
 a sulfated polysaccharide; and 
 fucoidan, or a suitable salt or derivative thereof. 
   
     
     
         2 . The composition of  claim 1 , wherein the composition is configured to exhibit a synergistic therapeutic effect on the endothelial glycocalyx of the mammal when administered thereto, the composition comprising:
 the one or more molecular precursor of endothelial glycocalyx in an amount of effective to enhance synthesis of new glycocalyx, enhance repair of damaged glycocalyx, and protect existing glycocalyx against damage, in the mammal to which the composition is administered;   the one or more antioxidant that associates with endothelial glycocalyx in an amount of effective to protect existing glycocalyx against damage, enhance synthesis of new glycocalyx, and enhance repair of damaged glycocalyx, and   the one or more glycocalyx mimetic in an amount of effective to enhance repair of damaged glycocalyx, enhance synthesis of new glycocalyx, and protect existing glycocalyx against damage.   
     
     
         3 . The composition of  claim 1 , wherein:
 the glucosamine, or suitable salt or derivative thereof, is include as glucosamine sulfate in an amount of at least about 375 mg;   the fucoidan, or suitable salt or derivative thereof, is included as fucoidan sulfate in an amount of at least about 106.25 mg;   the hyaluronan, or suitable salt or derivative thereof, is include as sodium hyaluronate in an amount of at least about 17.5 mg; and   total antioxidants, including the superoxide dismutase, or suitable transition metal conjugate or derivative thereof, are included in an amount of at least about 120 mg.   
     
     
         4 . A composition, comprising:
 one or more molecular precursor of endothelial glycocalyx, comprising glucosamine, or a suitable salt or derivative thereof;   one or more antioxidant that associates with endothelial glycocalyx, comprising superoxide dismutase, or a suitable transition metal conjugate or derivative thereof; and   one or more glycocalyx mimetic selected from the group consisting of:
 a nonsulfated glycosaminoglycan; 
 hyaluronan, or a suitable salt or derivative thereof; 
 a sulfated polysaccharide; and 
 fucoidan, or a suitable salt or derivative thereof. 
   
     
     
         5 . The composition of  claim 4 , further comprising one or more additional antioxidants selected from the group consisting of:
 catalase, or a suitable transition metal conjugate or derivative thereof; and   one or more polyphenols.   
     
     
         6 . The composition of  claim 4 , wherein the composition comprises:
 the hyaluronan, or suitable salt or derivative thereof; and   the fucoidan, or suitable salt or derivative thereof.   
     
     
         7 . The composition of  claim 6 , wherein at least one of:
 the glucosamine, or suitable salt or derivative thereof, is included as glucosamine sulfate,   the hyaluronan, or suitable salt or derivative thereof, is included as sodium hyaluronate; and   the fucoidan, or suitable salt or derivative thereof, is included as fucoidan sulfate.   
     
     
         8 . The composition of  claim 6 , wherein at least one of:
 the glucosamine, or suitable salt or derivative thereof, is selected from the group consisting of glucosamine sulfate, non-GMO vegetable glucosamine sulfate, non-GMO corn glucosamine sulfate, and D-glucosamine, or suitable salt or derivative thereof;   the superoxide dismutase, or suitable transition metal conjugate or derivative thereof, is selected from the group consisting of non-GMO plant, olive, artichoke, red grape, white grape, and melon superoxide dismutase, or suitable transition metal conjugate or derivative thereof; and   the hyaluronan, or suitable salt or derivative thereof, is selected from the group consisting of sodium hyaluronate, non-GMO microbial sodium hyaluronate, non-GMO  Streptoccoccus  sodium hyaluronate, non-GMO  Streptoccoccus equi  subsp.  Zooepidemicus  sodium hyaluronate, sodium hyaluronate having a purity of at least about 90% w/w, non-GMO microbial sodium hyaluronate having a purity of at least about 90% w/w, non-GMO  Streptoccoccus  sodium hyaluronate having a purity of at least about 90% w/w, and non-GMO  Streptoccoccus equi  subsp.  Zooepidemicus  sodium hyaluronate having a purity of at least about 90% w/w; and   the fucoidan, or suitable salt or derivative thereof, is selected from the group consisting of fucoidan sulfate, non-GMO plant, seaweed, or algae fucoidan sulfate, non-GMO  Laminaria  fucoidan sulfate, non-GMO  Laminaria japonica  fucoidan sulfate, fucoidan sulfate having a purity of at least about 85% w/w, non-GMO plant, seaweed, or algae fucoidan sulfate having a purity of at least about 85% w/w, non-GMO  Laminaria  fucoidan sulfate having a purity of at least about 85% w/w, and non-GMO  Laminaria japonica  fucoidan sulfate having a purity of at least about 85% w/w.   
     
     
         9 . The composition of  claim 6 , wherein:
 the glucosamine, or suitable salt or derivative thereof, is include as glucosamine sulfate in an amount of at least about 375 mg;   the fucoidan, or suitable salt or derivative thereof, is included as fucoidan sulfate in an amount of at least about 106.25 mg;   the hyaluronan, or suitable salt or derivative thereof, is include as sodium hyaluronate in an amount of at least about 17.5 mg; and   total antioxidants, including superoxide dismutase, or suitable transition metal conjugate or derivative thereof, are included in an amount of at least about 120 mg.   
     
     
         10 . The composition of  claim 6 , wherein:
 the glucosamine, or suitable salt or derivative thereof, is include as glucosamine sulfate in an amount of at least about 1500 mg;   the fucoidan, or suitable salt or derivative thereof, is included as fucoidan sulfate in an amount of at least about 425 mg;   the hyaluronan, or suitable salt or derivative thereof, is include as sodium hyaluronate in an amount of at least about 70 mg; and   total antioxidants, including the superoxide dismutase, or suitable transition metal conjugate or derivative thereof, are included in an amount of at least about 480 mg.   
     
     
         11 . The composition of  claim 9 , wherein the total antioxidants include:
 the superoxide dismutase, or a suitable transition metal conjugate or derivative thereof;   catalase, or a suitable transition metal conjugate or derivative thereof; and   one or more polyphenols.   
     
     
         12 . The composition of  claim 11 , wherein the superoxide dismutase, or suitable transition metal conjugate or derivative thereof, catalase, or suitable transition metal conjugate or derivative thereof, and one or more polyphenols are independently selected from the group consisting of non-GMO plant, olive, artichoke, red grape, white grape, and melon superoxide dismutase, catalase, and polyphenols. 
     
     
         13 . The composition of  claim 11 , wherein the catalase, or suitable transition metal conjugate or derivative thereof, is selected from the group consisting of iron(III)-conjugated catalase and iron(IV)-conjugated catalase. 
     
     
         14 . The composition of  claim 4 , wherein the superoxide dismutase, or suitable transition metal conjugate or derivative thereof, is selected from the group consisting of copper-conjugated superoxide dismutase, zinc-conjugated superoxide dismutase, extracellular superoxide dismutase, copper-conjugated extracellular superoxide dismutase, and zinc-conjugated extracellular superoxide dismutase. 
     
     
         15 . A method of manufacturing a composition that exhibits a synergistic therapeutic effect on the endothelial glycocalyx of a mammal when administered thereto, the method comprising preparing a mixture comprised of:
 one or more molecular precursor of endothelial glycocalyx in an amount of effective to increase production of endothelial glycocalyx in a mammal to which the composition is administered, the one or more molecular precursor of endothelial glycocalyx comprising glucosamine, or a suitable salt or derivative thereof   one or more antioxidant that associates with endothelial glycocalyx in an amount of effective to at least partially protect existing endothelial glycocalyx against damage caused by enzyme and/or oxidant in a mammal to which the composition is administered, the one or more antioxidant that associates with endothelial glycocalyx comprising superoxide dismutase, or a suitable transition metal conjugate or derivative thereof; and   one or more glycocalyx mimetic in an amount of effective to increase the density of endothelial glycocalyx at a site of endothelial glycocalyx damage in a mammal to which the composition is administered, the one or more glycocalyx mimetic selected from the group consisting of a nonsulfated glycosaminoglycan, preferably hyaluronan, or a suitable salt or derivative thereof, and a sulfated polysaccharide, preferably fucoidan, or a suitable salt or derivative thereof.   
     
     
         16 . The method of  claim 15 , wherein at least one of:
 the glucosamine, or suitable salt or derivative thereof, is selected from the group consisting of glucosamine sulfate, non-GMO vegetable glucosamine sulfate, non-GMO corn glucosamine sulfate, D-glucosamine;   the superoxide dismutase, or a suitable transition metal conjugate or derivative thereof, is selected from the group consisting of non-GMO plant, olive, artichoke, red grape, white grape, and melon superoxide dismutase; and   the hyaluronan, or suitable salt or derivative thereof, is selected from the group consisting of sodium hyaluronate, non-GMO microbial sodium hyaluronate, non-GMO  Streptoccoccus  sodium hyaluronate, non-GMO  Streptoccoccus equi  subsp.  Zooepidemicus  sodium hyaluronate, sodium hyaluronate having a purity of at least about 90% w/w, non-GMO microbial sodium hyaluronate having a purity of at least about 90% w/w, non-GMO  Streptoccoccus  sodium hyaluronate having a purity of at least about 90% w/w, and non-GMO  Streptoccoccus equi  subsp.  Zooepidemicus  sodium hyaluronate having a purity of at least about 90% w/w; and   the fucoidan, or suitable salt or derivative thereof, is selected from the group consisting of fucoidan sulfate, non-GMO plant, seaweed, or algae fucoidan sulfate, non-GMO  Laminaria  fucoidan sulfate, non-GMO  Laminaria japonica  fucoidan sulfate, fucoidan sulfate having a purity of at least about 85% w/w, non-GMO plant, seaweed, or algae fucoidan sulfate having a purity of at least about 85% w/w, non-GMO  Laminaria  fucoidan sulfate having a purity of at least about 85% w/w, and non-GMO  Laminaria japonica  fucoidan sulfate having a purity of at least about 85% w/w.   
     
     
         17 . The method of  claim 15 , wherein the mixture further comprises one or more additional antioxidants selected from the group consisting of:
 catalase, or a suitable transition metal conjugate or derivative thereof; and   one or more polyphenols.   
     
     
         18 . The method of  claim 17 , wherein the mixture comprises:
 glucosamine, or suitable salt or derivative thereof;   hyaluronan, or suitable salt or derivative thereof;   fucoidan, or suitable salt or derivative thereof;   superoxide dismutase, or suitable transition metal conjugate or derivative thereof;   catalase, or a suitable transition metal conjugate or derivative thereof; and   one or more polyphenols.   
     
     
         19 . The method of  claim 18 , wherein:
 the glucosamine, or suitable salt or derivative thereof, is in an amount of at least about 375 mg;   the fucoidan, or suitable salt or derivative thereof, is in an amount of at least about 106.25 mg;   the hyaluronan, or suitable salt or derivative thereof, is in an amount of at least about 17.5 mg; and   the superoxide dismutase, or suitable transition metal conjugate or derivative thereof, catalase, or suitable transition metal conjugate or derivative thereof, and one or more polyphenols are included in an amount of at least about 120 mg.   
     
     
         20 . The method of  claim 18 , wherein
 the glucosamine, or suitable salt or derivative thereof, is in an amount of at least about 1500 mg;   the fucoidan, or suitable salt or derivative thereof, is in an amount of at least about 425 mg;   the hyaluronan, or suitable salt or derivative thereof, is in an amount of at least about 70 mg; and   the superoxide dismutase, or suitable transition metal conjugate or derivative thereof, catalase, or suitable transition metal conjugate or derivative thereof, and one or more polyphenols are included in an amount of at least about 480 mg.