Composition and method for a prebiotic delivery system targeted to probiotic bacteria
View Patent ↗Provided herein is a particle made of a protein covalently bound to a prebiotic carbohydrate, thereby forming a conjugate, wherein at least two said conjugates are covalently crosslinked via their carbohydrate units (e.g. by a phospho-di-ester bond). The said particle may be used for selectively promoting probiotic bacteria growth in the colon and may be used to deliver additional probiotic growth factors, or other bioactives and drugs to the colon. Furthermore, provided herein are methods for preparing the particle, and for delivering a substance bound to, or entrapped within the particle, into the gastrointestinal tract of a subject in need thereof.
1 . A nutraceutical composition comprising a plurality of particles, each of the plurality of particles comprises a plurality of Maillard conjugates, wherein each Maillard conjugate comprises a peptide covalently bound to a prebiotic carbohydrate, wherein: said peptide is a lactoferrin peptide; wherein said prebiotic carbohydrate is selected from the group consisting of galacto-oligosaccharide, fructo-oligosaccharide, inulin, isomalto-oligosaccharide, soy-oligosaccharide, pectic-oligosaccharide, xylo-oligosaccharide and levan, or any combination thereof; at least one of: (i) a w/w ratio the peptide and the prebiotic carbohydrate within the plurality of Maillard conjugates is between 1:1 and 10:1; and (ii) a percentage of unreacted primary amino groups relative to a total amount of primary amino groups within the peptide is at most 50%; and wherein said particle is a core-shell micelle; and wherein at least 70% by weight of the core constitutes of the peptide and at least 70% by weight of the shell constitutes of the prebiotic carbohydrate; and wherein said nutraceutical composition is an oral dosage form.
2 . The nutraceutical composition particle of claim 1 , wherein the lactoferrin peptides in said plurality of Maillard conjugates are characterized by an average MW of about 5 KDa.
3 . The nutraceutical composition of claim 1 , wherein said peptide covalently bound to said prebiotic carbohydrate is via a primary amine of said peptide to a carbonyl of said prebiotic carbohydrate; and wherein the prebiotic carbohydrate has a degree of polymerization (DP) between 2 and 50.
4 . The nutraceutical composition of claim 1 , wherein said particle comprises at least two covalently linked Maillard conjugates.
5 . A nutraceutical composition comprising a plurality of particles, each of the plurality of particles consists of a plurality of Maillard conjugates, wherein each Maillard conjugate comprises a peptide covalently bound to a prebiotic carbohydrate, wherein: said peptide is a lactoferrin peptide and is characterized by water solubility of at least about 8% w/v at a pH of 10; said prebiotic carbohydrate is selected from galacto-oligosaccharide and fructo-oligosaccharide; a w/w ratio between the peptide and the prebiotic carbohydrate within the plurality of Maillard conjugates is between 1:1 and 10:1; a percentage of unreacted primary amino groups relative to a total amount of primary amino groups within the peptide is at most 50%; wherein said particle is a core-shell particle and wherein at least 70% by weight of the core constitutes of the peptide and at least 70% by weight of the shell constitutes of the prebiotic carbohydrate; wherein an average size of said plurality of particles is in the range of 10 nm to 1000 nm; and wherein said nutraceutical composition is an oral dosage form.
6 . The nutraceutical composition of claim 1 , wherein the average size of said micelle is in the range of 10 nm to 1000 nm.
7 . The nutraceutical composition of claim 5 , wherein said peptide is obtained via hydrolysis of lactoferrin by a human protease selected from the group consisting of: a gastric protease, an intestinal protease, and any combination thereof.
8 . The nutraceutical composition of claim 2 , wherein said core comprises at least 80% by weight of said peptide and said shell comprises at least 80% by weight of said prebiotic carbohydrate; and wherein said lactoferrin peptide is obtained via hydrolysis of lactoferrin by a human protease selected from pepsin, rennin, trypsin, and chymotrypsin, or any combination thereof.
9 . The nutraceutical composition of claim 2 , wherein said core, said shell, or both further comprises any one of: a prebiotic nutritional agent; a therapeutic agent, a nutraceutical, and a prebiotic growth factor.
10 . The nutraceutical composition comprising a nutritionally or a therapeutically effective amount of the plurality of particles according to claim 1 .
11 . The nutraceutical composition of claim 10 , wherein said composition is selected from the group consisting of: (i) in the form of an agglomerate of particles; (ii) in the form of a powder; and (iii) a suspension formulated for oral administration.