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AssigneeSolvotrin Therapeutics Ltd.
InventorsJohn Gilmer, Radics Gabor, Michael Whelehan, Jun Wang, Pat O'Flynn, Mark Ledwidge
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Compositions containing iron, buffering agent and denatured protein have been prepared that are capable of increasing serum iron in a subject. For example, spray dried microbeads have been prepared containing iron entrapped within a protein matrix and unbound iron in a buffered composition that provides a gastroprotective effect, preserves iron in the more available Fe2+ form and improves iron bioavailability in humans relative to previously known vehicles for delivering iron to a subject.
A composition comprising iron, buffering agent and a carrier comprising denatured protein, wherein the composition releases at least 71% of the total load of iron as ferrous iron over the course of one hour in simulated gastric fluid at pH 1.6, and wherein the composition when placed in simulated gastric fluid at pH 1.6 buffers the pH to at least 2 after 30 minutes, and wherein the composition when placed in a simulated intestinal fluid at pH 6.6 buffers the solution to at most pH 5.5 after 30 minutes, and wherein the composition, when administered orally to a human, has a relative trough to peak ratio of serum iron over 2 hours of at least 120% that of an equimolar dose of an orally administered immediate release ferrous sulfate composition.
A composition comprising iron and denatured protein core, an iron salt and a pH modifying agent wherein the composition releases at least 71% of its total load of iron in gastric conditions and at least 50% of its pH modifier and wherein the composition, when administered orally to a human, has a relative trough to peak Ratio of serum iron over 2 hours of at least 120% that of an equimolar dose of an orally administered ferrous sulfate composition.
A composition of the invention according to any preceding claim which releases at least 50% for example at least 71%, for example at least 75%, such as at least 80% of its buffering agent over the course of 30 minutes in simulated gastric fluid at pH 1.6.
A composition according to any preceding claim, which has an iron:protein ratio, by weight, of 1:50 to 5:1, for example 1:40 to 1:3.
A composition according to any preceding claim which has a total iron content of 2.5% to 50% by weight.
A composition according to any preceding claim which has a buffering agent:protein ratio, by weight, of 1:50 to 5:1, for example 1:40 to 1:3.
A composition according to any preceding claim which has a buffering agent:iron ratio, by weight, of 1:10 to 10:1, for example 1:3 to 3:1.
A composition according to any preceding claim which is substantially amorphous.
A composition according to any preceding claim wherein the denatured protein is at least 50%, 80% or 90% denatured.
A composition according to any preceding claim wherein the denatured protein may contain at least 50%, 80% or 90% denatured beta lactoglobulin.
A composition according to any preceding claim wherein the denatured protein has been subjected to a divalent metal iron removal process.
A composition according to any preceding claim wherein the water content of the composition is less than 20, less than 15%, or less than about 10% by weight.
A composition according to any preceding claim wherein the composition has a core which comprises a denatured aggregated protein matrix.
A composition according to any preceding claim wherein the composition has a core and a skin and the skin comprises a denatured aggregated protein and optionally, the skin further comprises a gelling agent.
A composition according to any preceding claim wherein the composition has a core and the core comprises a denatured aggregated protein matrix.
A composition according to any preceding claim wherein the denatured protein contains, excluding iron, less than 500 mg divalent metal ions per 100 g protein, such as less than 300 mg divalent metal ions per 100 g protein, for example 100 mg divalent metal ions per 100 g protein.
A composition according to any preceding claim wherein when administered orally to a human, has a Trough To Peak ratio of serum iron over 2 hours of at least 130%, 140%, 150%, 160% or 175% that of an equimolar dose of an orally administered immediate release ferrous sulfate composition.
A composition according to any preceding claim wherein when administered orally to a human, may have a trough to peak ratio of serum iron over 2 hours of at least 130%, 140% or 150% that of an equimolar dose of an orally administered immediate release ferrous sulfate composition.
A composition according to any preceding claim wherein the composition may release more than 70% for example more than 71 wt % of the total iron content as ferrous iron over the course of 15 minutes, or 30 minutes, or 45 minutes, or 60 minutes in simulated gastric fluid at pH 1.6;
A composition according to any preceding claim wherein the composition further comprises a stabilizer, such as ascorbic acid, ascorbates, for example a stabilizer selected from L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) or combinations thereof.
A composition according to any preceding claim wherein the iron:protein ratio is 1:20 to 1:3, for example 1:40 to 1:3, such as 1:15 to about 1 to 4 such as about 1:6 to about 1:12.
A composition according to any preceding claim wherein the composition consists of particles having an average particle size of 2000 microns or less, 1000 microns or less, 600 microns or less, 500 microns or less, or 300 microns or less, or 100 microns or less or 80 microns or less or 60 microns or less, or 40 microns or less or 20 microns or less.
A composition according to any preceding claim wherein the iron in the composition comprises at least 10%, 25%, 50%, 75%, 90%, 95%, 98% or 99% ferrous iron.
A composition according to any preceding claim wherein the composition is stable with respect to ferrous iron content and microbiological burden, for at least 6 months when stored in a sealed container at accelerated storage conditions (40° C. and 75% Relative Humidity).
A composition according to any preceding claim wherein the composition is stable with respect to ferrous iron content when stored in a sealed container at ambient conditions for at least 24 months.
A composition according to any preceding claim wherein, the denatured protein comprises denatured whey protein, denatured whey protein isolate, denatured beta lactoglobulin, or combinations thereof.
A composition according to any preceding claim wherein the composition comprises (as buffering agent or pH modifier) a salt, for example a salt of a short chain fatty acid, such as a salt of a C2 to C5 fatty acid.
A composition according to any preceding claim wherein the composition comprises (as buffering agent or pH modifier) at least one of phosphoric acid, a salt, including a salt selected from acetates, propionates, butyrates, phosphates, and citrates including a monovalent salt such as a sodium salt.
A composition according to any preceding claim wherein the buffering agent or pH modifier is present in an amount by weight of greater than about 3% such as greater than about 4%, such as greater than about 5%, for example greater than about 6%, such as greater than about 7% such as greater than about 8%, for example greater than about 10%, such as greater than about 12%, for example greater than about 15% such as about 17%.
A composition according to any preceding claim formed from a liquid composition comprising denatured protein, a buffering agent such as a salt, and iron wherein the denatured protein is desirably present in an amount from 5% to 80%;
A composition according to any preceding claim wherein in the composition the buffering agent is desirably present in an amount from 5% to 50%;
A composition according to any preceding claim wherein the denatured protein contains less than 500 mg Calcium per 100 g of total protein, 300 mg Calcium per 100 g of total protein, for example, less than 200 mg Calcium per 100 g of total protein, for example less than 100 mg Calcium per 100 g of total protein.
A composition according to any preceding claim comprising a core of dehydrated iron protein hydrogel.
A composition comprising:
A method of increasing the serum iron in a mammal in need thereof comprising administering a composition comprising
A composition comprising iron and a buffering agent, wherein the composition releases at least 70% for example at least 71% of the total load of iron as ferrous iron over the course of 30 minutes in simulated gastric fluid at pH 1.6, and wherein the composition when placed in simulated gastric fluid at pH 1.6 buffers the pH to at least 2, and wherein the composition when placed in the simulated intestinal fluid at pH 6.6 buffers the solution to at most pH 5.5, and wherein the composition, when administered orally to a human, has a relative Trough To Peak Ratio of serum iron over 2 hours of at least 120% that of an equimolar dose of an orally administered immediate release ferrous sulfate composition.
A composition comprising iron, buffering agent and a carrier wherein the buffering agent is present in an amount by weight of greater than about 3% such as greater than about 4%, such as greater than about 5%, for example greater than about 6%, such as greater than about 7% such as greater than about 8%, for example greater than about 10%, such as greater than about 12%, for example greater than about 15% such as about 17% by weight of the composition.
A process for producing a dry material for delivery of iron;
Dependencies are inferred from the claim text.