Compounds to modulate intestinal absorption of nutrients
This disclosure relates to compositions including formulated sucralfate or other aluminum-crosslinked sulfated agents for the modulation of nutrient absorption through the intestinal lining as well as methods for the manufacture of and the use of these compounds for treating disorders requiring a modulation of certain nutrients to the body including diabetes type II and clinical obesity.
1. A composition comprising particles comprising an acidified aluminum cross-linked sulfated agent and a particle stabilizer cross-linked together with a sulfated humectant agent, wherein the aluminum/sulfate ratio in the composition is about 1 to about 2, and wherein the particle stabilizer and sulfated humectant agent can be the same material.
2. The composition of claim 1 , wherein the aluminum cross-linked sulfated agent is sucralfate.
3. The composition of claim 1 , further comprising a liquid carrier.
4. The composition of claim 1 , further comprising a pH-sensitive material.
5. The composition of claim 1 , further comprising carrageenan, propylene glycol, 1,2,6-hexanetriol, butylene glycol, dipropylene glycol, hexylene glycol, glycerin, triethylene glycol, erythritol capryl glycol, phytantriol, hexanediol beeswax, hexanetriol beeswax, panthenol, sodium pyrollidone carboxylic acid, hyaluronic acid, inositol, glycogen, sorbitol, polyglyceryl sorbitol, glucose, fructose, xylitol, elastin, collagen, silk, keratin, isoceteth, isolaureth, laneth, laureth, steareth, polyethylene glycol, silicon copolymers, ammonium lactate, glyceryl triacetate, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed keratin, hydrolyzed silk, lactic acid, mannitol, panthenol, polydextrose, propylene glycerol, quilaia, urea, or betaine.
6. The composition of claim 1 , wherein the sulfated humectant agent is selected from the group consisting of sulfated dextran, sulfated dextrin, sulfated amylopectin, sulfated amylose, sulfated cellulose, carrageenan, chondroitin sulfate, glucose sulfate, sucrose sulfate, and raffinose sulfate.
7. The composition of claim 6 , wherein the sulfated humectant agent is carrageenan.
8. The composition of claim 1 , wherein the particle stabilizer is selected from the group consisting of phosphate ions, pectin, carrageenan, chitosan, cellulose derivatives, gellan gum, alginate, gum karaya, dextran, pullulan, polyethylene glycol (PEG), polyvinyl alcohol (PVA), beeswax, sodium borate, stearic acid, carbomer, cetyl alcohol, propylene glycol, polysorbate, lecithin, glyceryl monostearate, acetic esters of fatty acid, lactic esters of fatty acid, citric esters of fatty acid, tartaric esters of fatty acid, acetyltartaric esters of fatty acid, sucroglycerides, polyglycerol esters of fatty acid, propane-2,3-diol esters of fatty acid, sodium stearoyl-2-lactylate, calcium stearoyl-2-lactylate, stearyl tartate, and castor oil derivatives.
9. The composition of claim 8 , wherein the particle stabilizer comprises phosphate ions.
10. The composition of claim 1 in dry form.
11. The composition of claim 10 , wherein the composition can be re-hydrated with an acidic liquid while retaining particle size within 20%.
12. The composition of claim 1 , wherein the particles range in size from about 0.1 to about 500 microns.
13. The composition of claim 1 , wherein the composition is a dry mucoadhesive composition that following hydration with an acidic liquid stably adheres to a mucin coated surface under shear stress conditions.
14. The composition of claim 1 , wherein when hydrated with an acidic liquid, the composition forms a barrier that when prepared at 10 mg/ml and applied to 1 cm 2 surface area cellulose nitrate filter with 0.45 micron holes in a Franz diffusion chamber exhibits less than 60% permeation of glucose 5 minutes after addition of 120 g/L glucose solution to the top chamber at a pH of 1.
15. The composition of claim 1 , wherein the composition releases <0.5% aluminum by weight in the presence of stomach acid or simulated gastric fluid and when administered to a subject forms an effective nutrient barrier in the proximal gastrointestinal tract.
16. The composition of claim 1 , wherein the sulfated humectant agent is incorporated into the particles prior to particle formation.
17. The composition of claim 1 , wherein the sulfated humectant agent is fully integrated into the particles via electrostatic interaction.
18. The composition of claim 1 , wherein the composition has a viscosity greater than 35 Pa·s after being dried and rehydrated.
19. The composition of claim 1 in liquid form.
20. The composition of claim 19 , wherein the composition has a viscosity greater than 35 Pa·s.
21. The composition of claim 1 , wherein the aluminum/sulfate ratio in the composition is about 1.72.
22. The composition of claim 1 , wherein the aluminum/sulfate ratio in the composition is about 1.83.
23. A composition comprising particles comprising an acidified aluminum cross-linked sulfated agent and a particle stabilizer cross-linked together with a humectant, wherein the aluminum/sulfate ratio in the composition is about 1 to about 2, wherein the particle stabilizer comprises phosphate ions, and wherein the particle stabilizer and humectant can be the same material.
24. The composition of claim 23 , wherein the aluminum cross-linked sulfated agent is sucralfate.
25. The composition of claim 23 , wherein the humectant is a sulfated agent.
26. The composition of claim 23 , wherein the humectant comprises carrageenan, propylene glycol, 1,2,6-hexanetriol, butylene glycol, dipropylene glycol, hexylene glycol, glycerin, triethylene glycol, erythritol capryl glycol, phytantriol, hexanediol beeswax, hexanetriol beeswax, panthenol, sodium pyrollidone carboxylic acid, hyaluronic acid, inositol, glycogen, sorbitol, polyglyceryl sorbitol, glucose, fructose, xylitol, elastin, collagen, silk, keratin, isoceteth, isolaureth, laneth, laureth, steareth, polyethylene glycol, silicon copolymers, ammonium lactate, glyceryl triacetate, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed keratin, hydrolyzed silk, lactic acid, mannitol, panthenol, polydextrose, propylene glycerol, quilaia, urea, or betaine.
27. The composition of claim 23 , further comprising phosphate ions, pectin, carrageenan, chitosan, cellulose derivatives, gellan gum, alginate, gum karaya, dextran, pullulan, polyethylene glycol (PEG), polyvinyl alcohol (PVA), beeswax, sodium borate, stearic acid, carbomer, cetyl alcohol, propylene glycol, polysorbate, lecithin, glyceryl monostearate, acetic esters of fatty acid, lactic esters of fatty acid, citric esters of fatty acid, tartaric esters of fatty acid, acetyltartaric esters of fatty acid, sucroglycerides, polyglycerol esters of fatty acid, propane-2,3-diol esters of fatty acid, sodium stearoyl-2-lactylate, calcium stearoyl-2-lactylate, stearyl tartate, or castor oil derivatives.
28. The composition of claim 23 , wherein the particles range in size from about 0.1 to about 500 microns.
29. A composition comprising particles comprising an acidified aluminum cross-linked sulfated agent and a particle stabilizer cross-linked together with a humectant, wherein the aluminum/sulfate ratio in the composition is about 1 to about 2, wherein the composition is in dry form, and wherein the composition can be re-hydrated with an acidic liquid while retaining particle size within 20%.
30. The composition of claim 29 , wherein the aluminum cross-linked sulfated agent is sucralfate.
31. The composition of claim 29 , wherein the humectant comprises carrageenan, propylene glycol, 1,2,6-hexanetriol, butylene glycol, dipropylene glycol, hexylene glycol, glycerin, triethylene glycol, erythritol capryl glycol, phytantriol, hexanediol beeswax, hexanetriol beeswax, panthenol, sodium pyrollidone carboxylic acid, hyaluronic acid, inositol, glycogen, sorbitol, polyglyceryl sorbitol, glucose, fructose, xylitol, elastin, collagen, silk, keratin, isoceteth, isolaureth, laneth, laureth, steareth, polyethylene glycol, silicon copolymers, ammonium lactate, glyceryl triacetate, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed keratin, hydrolyzed silk, lactic acid, mannitol, panthenol, polydextrose, propylene glycerol, quilaia, urea, or betaine.
32. The composition of claim 29 , wherein the particle stabilizer is selected from the group consisting of phosphate ions, pectin, carrageenan, chitosan, cellulose derivatives, gellan gum, alginate, gum karaya, dextran, pullulan, polyethylene glycol (PEG), polyvinyl alcohol (PVA), beeswax, sodium borate, stearic acid, carbomer, cetyl alcohol, propylene glycol, polysorbate, lecithin, glyceryl monostearate, acetic esters of fatty acid, lactic esters of fatty acid, citric esters of fatty acid, tartaric esters of fatty acid, acetyltartaric esters of fatty acid, sucroglycerides, polyglycerol esters of fatty acid, propane-2,3-diol esters of fatty acid, sodium stearoyl-2-lactylate, calcium stearoyl-2-lactylate, stearyl tartate, and castor oil derivatives.
33. The composition of claim 29 , wherein the particles range in size from about 0.1 to about 500 microns.
34. The composition of claim 29 , wherein the humectant is a sulfated agent.
35. The composition of claim 34 , wherein the sulfated humectant agent is selected from the group consisting of sulfated dextran, sulfated dextrin, sulfated amylopectin, sulfated amylose, sulfated cellulose, carrageenan, chondroitin sulfate, glucose sulfate, sucrose sulfate, and raffinose sulfate.
36. The composition of claim 35 , wherein the sulfated humectant agent is carrageenan.