US2023330131A1PendingUtilityA1
Prebiotic composition and its use

Assignee: CP KELCO US INCPriority: Jan 18, 2019Filed: Mar 3, 2023Published: Oct 19, 2023
Est. expiryJan 18, 2039(~12.5 yrs left)· nominal 20-yr term from priority
Inventors:Neil A. Morrison Hailong Yu John P. Abdou Narayana Murthy Manjunatha Todd A. Talashek
A61K 35/747A61K 35/745A61K 31/715A61K 9/0053A61P 1/14C08B 37/006A23L 33/125A23L 29/272A23L 33/21A23L 29/269A61K 31/716A61K 31/702A61P 37/02A23V 2002/00C08L 5/00
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Claims
Abstract

Disclosed herein is an ingestible composition comprising a sphingan and its use as a prebiotic.
Claims

exact text as granted — not AI-modified
1 . An ingestible composition comprising a prebiotic effective amount of a sphingan. 
     
     
         2 . The ingestible composition of  claim 1 , wherein the amount of the sphingan is selected from about 1 g to about 10 g, about 1 g to about 9 g, about 1 g to about 8 g, about 1 g to about 7 g, about 1 g to about 6 g, about 1 g to about 5 g, about 1 g to about 4 g, about 1 g to about 3 g, or about 2 g. 
     
     
         3 . The ingestible composition of  claim 1 , wherein the sphingan comprises a high, intermediate, or low acyl sphingan selected from a high acyl gellan, an intermediate acyl gellan, a low acyl gellan, a high acyl welan, an intermediate acyl welan, a low acyl welan, a high acyl rhamsan, an intermediate acyl rhamsan, a low acyl rhamsan, a high acyl diutan, an intermediate acyl diutan, a low acyl diutan, S-88, S-198, S-7, or a combination thereof. 
     
     
         4 . The ingestible composition of  claim 1 , wherein the sphingan comprises a high acyl sphingan polysaccharide, an intermediate acyl sphingan polysaccharide, a low acyl sphingan polysaccharide, or a combination thereof. 
     
     
         5 . The ingestible composition of  claim 1 , wherein the sphingan comprises a high acyl sphingan oligosaccharide, an intermediate acyl sphingan oligosaccharide, a low acyl sphingan oligosaccharide, or a combination thereof. 
     
     
         6 . The ingestible composition of  claim 1 , wherein the sphingan comprises a high, intermediate, or low acyl sphingan oligosaccharide (SOS) obtained by a process, which comprises:
 preparing a first composition comprising a high/intermediate/low acyl sphingan or a high/intermediate/low acyl sphingan polysaccharide and a liquid medium;   hydrolyzing a glycosidic bond of the high/intermediate/low acyl sphingan or the high/intermediate/low acyl sphingan polysaccharide to obtain a second composition;   subjecting the second composition to ultrafiltration, size-exclusion chromatography, precipitation, centrifugation, or a combination thereof to obtain a third composition comprising the high/intermediate/low acyl SOS; and   optionally, isolating or recovering the third composition.   
     
     
         7 . The ingestible composition of  claim 1 , wherein the sphingan comprises a high/intermediate/low sphingan oligosaccharide selected from:
 (i) a composition comprising Glc,GlcA, Glc,GlcA,Glyc, Glc,GlcA,Rha, Glc,GlcA,Rha,Glyc, Glc,GlcA,Rha,-H2O, Glc,Rha, Glc,Rha+28, Glc2,GlcA, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA,Rha,Ac, Glc2,GlcA,Rha,Glyc, Glc2,GlcA,Rha,Glyc,+28, Glc2,GlcA,Rha,Glyc.-H2O, Glc2,GlcA, Rha,-H2O, Glc2,GlcA,Rha2,Glyc, Glc2,GlcA2,Rha, Glc2,GlcA2, Rha2,Ac2,Glyc2,-H2O, Glc2,Rha, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2,Glyc, Glc3,GlcA2,Rha, Glc3,GlcA2,Rha,Glyc, Glc3,GlcA2,Rha2,Glyc, Glc3,GlcA3,Rha2, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,+43, Glc4,GlcA,Rha2,Ac, Glyc, Glc4,GlcA2,Rha, Glc4,GlcA2,Rha,Ac,Glyc,-H2O, Glc4,GlcA2,Rha,Ac,Glyc2, Glc4,GlcA2,Rha2,Ac,Glyc, Glc4,GlcA2,Rha2,Glyc, Glc4,GlcA3,Rha2, Glc4,GlcA2,Rha3,Ac, Glc4,GlcA3,Rha2/Glc4,GlcA2,Rha2,Glyc2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2,Ac, Glc5,GlcA4,Rha2, Glc6,GlcA3,Rha3, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), Glcx,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   (ii) a composition comprising a tetramer (Glc,GlcA,Glc,Rha), a tetramer (Glc,GlcA,Glc,Rha) with acetate and/or glycerate, an octamer (Glc,GlcA,Glc,Rha,Glc,GlcA,Glc,Rha), an octamer (Glc,GlcA,Glc,Rha,Glc,GlcA,Glc,Rha) with acetate and/or glycerate, Glc,GlcA,Glc, Rha,Glc,GlcA, Glc,Rha;   (iii) a composition comprising a tetramer (Glc,GlcA,Glc,Rha), an octamer (Glc,GlcA,Glc,Rha,Glc,GlcA,Glc,Rha), a pentamer (Glc,GlcA,Glc,Rha,Glc), GlcA,Glc,Rha, Glc,GlcA,Glc, Glc,GlcA;   (iv) a composition comprising Glc(Glc-Glc),GlcA, Glc(Glc-Glc), GlcA,Glc, Glc,Glc;   (v) a composition comprising a tetramer (Glc,GlcA,Glc,Rha), GlcA,Glc,(Rha-Rha), Glc,(Rha-Rha),Rha, GlcA,Glc,Rha, Glc,GlcA,Glc, Rha,Glc, GlcA,Glc;   (vi) a composition comprising Glc,GlcA, Glc,GlcA,Glyc, Glc,GlcA,Rha, Glc,GlcA,Rha,Glyc, Glc,Rha, Glc,Rha+28, Glc2,GlcA, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA,Rha,Ac, Glc2,GlcA,Rha,Glyc, Glc2,GlcA,Rha,Glyc,+28, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2,Glyc, Glc3,GlcA2,Rha,Glyc, Glc3,GlcA2,Rha2,Glyc, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,Ac, Glyc, Glc4,GlcA2,Rha2,Ac,Glyc, Glc4,GlcA2,Rha2,Glyc, Glc4,GlcA2,Rha3,Ac, Glc4,GlcA3,Rha2/Glc4,GlcA2,Rha2,Glyc2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2,Ac, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   (vii) a composition comprising Glc,GlcA, Glc,GlcA,Rha, Glc,Rha, Glc,Rha+28, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA2,Rha, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA2,Rha, Glc3,GlcA3,Rha2, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,+43, Glc4,GlcA2,Rha, Glc4,GlcA3,Rha2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2, Glc5,GlcA4,Rha2, Glc6,GlcA3,Rha3, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   (viii) a composition comprising Glc,GlcA,Rha,-H2O, Glc,Rha, Glc2,GlcA,Rha,-H2O, Glc2,Rha;   (ix) a composition comprising Glc,GlcA, Glc,GlcA,Glyc, Glc,GlcA,Rha, Glc,GlcA,Rha,Glyc, Glc,Rha, Glc,Rha+28, Glc2,GlcA, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA,Rha,Ac, Glc2,GlcA,Rha,Glyc, Glc2,GlcA,Rha,Glyc,+28, Glc2,GlcA,Rha,Glyc.-H2O, Glc2,GlcA,Rha2,Glyc, Glc2,GlcA2, Rha2,Ac2,Glyc2,-H2O, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2,Glyc, Glc3,GlcA2,Rha,Glyc, Glc3,GlcA2,Rha2,Glyc, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,+43, Glc4,GlcA,Rha2,Ac, Glyc, Glc4,GlcA2,Rha,Ac,Glyc,-H2O, Glc4,GlcA2,Rha,Ac,Glyc2, Glc4,GlcA2,Rha2,Ac,Glyc, Glc4,GlcA2,Rha2,Glyc, Glc4,GlcA3,Rha2, Glc4,GlcA2,Rha3,Ac, Glc4,GlcA3,Rha2/Glc4,GlcA2,Rha2,Glyc2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2,Ac, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   or a combination thereof.   
     
     
         8 . A method for
 (A) promoting beneficial bacterial growth in the colon of a mammal, said method comprising ingesting on an effective schedule a beneficial bacterial growth effective amount of a sphingan and an ingestible medium;   (B) decreasing propionate and/or increasing butyrate levels in the colon of a mammal, said method comprising: ingesting on an effective schedule a composition comprising an effective amount of a sphingan and an ingestible medium;   (C) improving intestinal barrier integrity in the colon of a mammal, said method comprising: ingesting on an effective schedule a composition comprising an intestinal barrier integrity effective amount of a sphingan and an ingestible medium; or   (D) reducing levels of TNF-α and/or IL-8 in the colon of a mammal, said method comprising: ingesting on an effective schedule a composition comprising a TNF-α and/or IL-8 reducing effective amount of a sphingan and an ingestible medium.   
     
     
         9 . The method of  claim 8 , wherein the mammal is a human and the amount of the sphingan is selected from about 10 mg/kg to about 150 mg/kg, about 10 mg/kg to about 140 mg/kg, about 10 mg/kg to about 130 mg/kg, about 10 mg/kg to about 120 mg/kg, about 10 mg/kg to about 110 mg/kg, about 10 mg/kg to about 100 mg/kg, about 10 mg/kg to about 90 mg/kg, about 10 mg/kg to about 80 mg/kg, about 10 mg/kg to about 70 mg/kg, about 10 mg/kg to about 60 mg/kg, 10 mg/kg to about 50 mg/kg, about 10 mg/kg to about 40 mg/kg, or about 20 mg/kg to about 30 mg/kg of the human ingesting the composition. 
     
     
         10 . The method of  claim 8 , wherein the sphingan comprises a high, intermediate, or low acyl sphingan selected from a high acyl gellan, an intermediate acyl gellan, a low acyl gellan, a high acyl welan, an intermediate acyl welan, a low acyl welan, a high acyl rhamsan, an intermediate acyl rhamsan, a low acyl rhamsan, a high acyl diutan, an intermediate acyl diutan, a low acyl diutan, S-88, S-198, S-7, or a combination thereof. 
     
     
         11 . The method of  claim 8 , wherein the sphingan comprises a high acyl sphingan polysaccharide, an intermediate acyl sphingan polysaccharide, a low acyl sphingan polysaccharide, or a combination thereof. 
     
     
         12 . The method of  claim 8 , wherein the sphingan comprises a high acyl sphingan oligosaccharide, an intermediate acyl oligosaccharide, a low acyl sphingan oligosaccharide, or a combination thereof. 
     
     
         13 . The method of  claim 8 , wherein the sphingan comprises a high, intermediate, or low acyl sphingan oligosaccharide (SOS) obtained by a process, which comprises:
 preparing a first composition comprising a high/intermediate/low acyl sphingan or a high/intermediate/low acyl sphingan polysaccharide and a liquid medium;   hydrolyzing a glycosidic bond of the high/intermediate/low acyl sphingan or the high/intermediate/low acyl sphingan polysaccharide to obtain a second composition;   subjecting the second composition to ultrafiltration, size-exclusion chromatography, precipitation, centrifugation, or a combination thereof to obtain a third composition comprising the high/intermediate/low acyl SOS; and   optionally, isolating or recovering the third composition.   
     
     
         14 . The method of  claim 8 , wherein the sphingan comprises a high/intermediate/low acyl sphingan oligosaccharide selected from
 (i) a composition comprising Glc,GlcA, Glc,GlcA,Glyc, Glc,GlcA,Rha, Glc,GlcA,Rha,Glyc, Glc,GlcA,Rha,-H2O, Glc,Rha, Glc,Rha+28, Glc2,GlcA, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA,Rha,Ac, Glc2,GlcA,Rha,Glyc, Glc2,GlcA,Rha,Glyc,+28, Glc2,GlcA,Rha,Glyc.-H2O, Glc2,GlcA, Rha,-H2O, Glc2,GlcA,Rha2,Glyc, Glc2,GlcA2,Rha, Glc2,GlcA2, Rha2,Ac2,Glyc2,-H2O, Glc2,Rha, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2,Glyc, Glc3,GlcA2,Rha, Glc3,GlcA2,Rha,Glyc, Glc3,GlcA2,Rha2,Glyc, Glc3,GlcA3,Rha2, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,+43, Glc4,GlcA,Rha2,Ac, Glyc, Glc4,GlcA2,Rha, Glc4,GlcA2,Rha,Ac,Glyc,-H2O, Glc4,GlcA2,Rha,Ac,Glyc2, Glc4,GlcA2,Rha2,Ac,Glyc, Glc4,GlcA2,Rha2,Glyc, Glc4,GlcA3,Rha2, Glc4,GlcA2,Rha3,Ac, Glc4,GlcA3,Rha2/Glc4,GlcA2,Rha2,Glyc2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2,Ac, Glc5,GlcA4,Rha2, Glc6,GlcA3,Rha3, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), Glcx,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   (ii) a composition comprising a tetramer (Glc,GlcA,Glc,Rha), a tetramer (Glc,GlcA,Glc,Rha) with acetate and/or glycerate, an octamer (Glc,GlcA,Glc,Rha,Glc,GlcA,Glc,Rha), an octamer (Glc,GlcA,Glc,Rha,Glc,GlcA,Glc,Rha) with acetate and/or glycerate, Glc,GlcA,Glc, Rha,Glc,GlcA, Glc,Rha;   (iii) a composition comprising a tetramer (Glc,GlcA,Glc,Rha), an octamer (Glc,GlcA,Glc,Rha,Glc,GlcA,Glc,Rha), a pentamer (Glc,GlcA,Glc,Rha,Glc), GlcA,Glc,Rha, Glc,GlcA,Glc, Glc,GlcA;   (iv) a composition comprising Glc(Glc-Glc),GlcA, Glc(Glc-Glc), GlcA,Glc, Glc,Glc;   (v) a composition comprising a tetramer (Glc,GlcA,Glc,Rha), GlcA,Glc,(Rha-Rha), Glc,(Rha-Rha),Rha, GlcA,Glc,Rha, Glc,GlcA,Glc, Rha,Glc, GlcA,Glc;   (vi) a composition comprising Glc,GlcA, Glc,GlcA,Glyc, Glc,GlcA,Rha, Glc,GlcA,Rha,Glyc, Glc,Rha, Glc,Rha+28, Glc2,GlcA, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA,Rha,Ac, Glc2,GlcA,Rha,Glyc, Glc2,GlcA,Rha,Glyc,+28, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2,Glyc, Glc3,GlcA2,Rha,Glyc, Glc3,GlcA2,Rha2,Glyc, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,Ac, Glyc, Glc4,GlcA2,Rha2,Ac,Glyc, Glc4,GlcA2,Rha2,Glyc, Glc4,GlcA2,Rha3,Ac, Glc4,GlcA3,Rha2/Glc4,GlcA2,Rha2,Glyc2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2,Ac, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   (vii) a composition comprising Glc,GlcA, Glc,GlcA,Rha, Glc,Rha, Glc,Rha+28, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA2,Rha, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA2,Rha, Glc3,GlcA3,Rha2, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,+43, Glc4,GlcA2,Rha, Glc4,GlcA3,Rha2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2, Glc5,GlcA4,Rha2, Glc6,GlcA3,Rha3, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   (viii) a composition comprising Glc,GlcA,Rha,-H2O, Glc,Rha, Glc2,GlcA,Rha,-H2O, Glc2,Rha;   (ix) a composition comprising Glc,GlcA, Glc,GlcA,Glyc, Glc,GlcA,Rha, Glc,GlcA,Rha,Glyc, Glc,Rha, Glc,Rha+28, Glc2,GlcA, Glc2,GlcA,Rha, Glc2,GlcA,Rha,+28, Glc2,GlcA,Rha,Ac, Glc2,GlcA,Rha,Glyc, Glc2,GlcA,Rha,Glyc,+28, Glc2,GlcA,Rha,Glyc.-H2O, Glc2,GlcA,Rha2,Glyc, Glc2,GlcA2, Rha2,Ac2,Glyc2,-H2O, Glc3,GlcA,Rha, Glc3,GlcA,Rha2, Glc3,GlcA,Rha2,Glyc, Glc3,GlcA2,Rha,Glyc, Glc3,GlcA2,Rha2,Glyc, Glc3,GlcA3,Rha2, Glc4,GlcA,Rha2,+43, Glc4,GlcA,Rha2,Ac, Glyc, Glc4,GlcA2,Rha,Ac,Glyc,-H2O, Glc4,GlcA2,Rha,Ac,Glyc2, Glc4,GlcA2,Rha2,Ac,Glyc, Glc4,GlcA2,Rha2,Glyc, Glc4,GlcA3,Rha2, Glc4,GlcA2,Rha3,Ac, Glc4,GlcA3,Rha2/Glc4,GlcA2,Rha2,Glyc2, Glc5,GlcA2,Rha2, Glc5,GlcA2,Rha2,Ac, Glc(Ac/Glyc)x,GlcAx,Glcx,Rhax (where x is 4 to about 25), or a combination thereof;   or a combination thereof.   
     
     
         15 . The method of  claim 8 , wherein the sphingan comprises a native sphingan and the bacteria is Bifidobacteriaceae. 
     
     
         16 . The method of  claim 15 , wherein the sphingan comprises a gellan gum. 
     
     
         17 . The method of  claim 8 , wherein the mammal is a human and the Bifidobacteriaceae levels increase in the lumen of the proximal colon range from (a) about 20% to about 180% during treatment compared to control or (b) from about 330% to about 590% during treatment compared to untreated control. 
     
     
         18 . The method of  claim 8 , wherein the mammal is a human and the sphingan comprises a high/low acyl sphingan oligosaccharide and the bacteria is  Blautia ,  Parabacteroides ,  Faecalibacterium ,  Clostridium  XVIII, or a combination thereof. 
     
     
         19 . The method of  claim 18 , wherein one or more of the following occurs:
 (a) the  Blautia  levels increase up to at least about 5-fold compared to untreated control   (b) the  Parabacteroides  levels increase from about 2-fold to about 40-fold compared to untreated control.   (c) the  Faecalibacterium  levels increase from about 10-fold to about 190-fold during treatment compared to untreated control, and   (d) the  Clostridium  XVIII levels increase from about 12-fold to about 60-fold compared to untreated control.   
     
     
         20 . A process for preparing a high/intermediate/low acyl sphingan oligosaccharide (“SOS”) of  claim 5 , which comprises:
 preparing a first composition comprising a high/intermediate/low acyl sphingan or a high/intermediate/low acyl sphingan polysaccharide and a liquid medium; 
 hydrolyzing a glycosidic bond of the high/intermediate/low acyl sphingan or the high/intermediate/low acyl sphingan polysaccharide to obtain a second composition; 
 subjecting the second composition to ultrafiltration, size-exclusion chromatography, precipitation, centrifugation, or a combination thereof to obtain a third composition comprising the high/intermediate/low acyl SOS; and 
 optionally, isolating or recovering the third composition. 
 
     
     
         21 . The process of  claim 20 , wherein said hydrolyzing is mediated by an acid, an enzyme, sonication, high-pressure homogenization, radiation, or a combination thereof. 
     
     
         22 . The process of  claim 21 , wherein the enzyme is a gellanase, a rhamnogalacturonan endolyase (EC 4.2.2.23), a rhamnogalacturonan exolyase (EC 4.2.2.24), a gellan lyase (EC 4.2.2.25), or a combination thereof. 
     
     
         23 . The process of  claim 21 , wherein said subjecting comprises filtering the second composition through a membrane having a molecular weight cutoff of either about 5 kDa or about 10 kDa to obtain a filtrate comprising the third composition. 
     
     
         24 . A composition comprising the SOS as prepared by  claim 20 .
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