Therapeutic carbon monoxide formulations
A pharmaceutical composition is described that includes a pharmaceutical carrier comprising gas pockets containing carbon monoxide gas, wherein the pharmaceutical carrier is a foam, a solid, or a hydrogel. Methods of using the pharmaceutical composition to treat an inflammatory disease or condition, and methods of making the pharmaceutical composition, are also described.
1 . A pharmaceutical composition, comprising a pharmaceutical carrier comprising gas pockets containing carbon monoxide gas having a concentration of at least 0.5 mg/g, as measured by gas-chromatography thermal conductivity, wherein the pharmaceutical carrier is a foam or a hydrogel comprising xanthan gum, methylcellulose and maltodextrin, wherein the ratio of methylcellulose to maltodextrin is from 0:6:1 to 1:1 w/w and the ratio of maltodextrin to xanthan gum is from 2.5:1 to 1.5 to 1, or a solid sugar matrix comprising glucose, fructose, sucrose, lactose, maltose, isomaltose, corn syrup or mixtures thereof.
2 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition provides extended release of carbon monoxide gas.
3 . The composition of claim 1 , wherein the pharmaceutical carrier is a foam.
4 . The composition of claim 1 , wherein the foam comprises from 0.4% to 0.6% xanthan gum by weight.
5 . The composition of claim 1 , wherein the pharmaceutical carrier is a solid sugar matrix.
6 . The composition of claim 5 , wherein the sugar comprises sucrose and lactose.
7 . The composition of claim 1 , wherein the pharmaceutical carrier is a hydrogel.
8 . The composition of claim 1 , wherein the pharmaceutical carrier is a foam or a hydrogel and further comprises alginate.
9 . The composition of claim 1 , wherein the pharmaceutical composition is a stable composition.
10 . The composition of claim 1 , wherein the concentration of carbon monoxide gas is at least 0.8 mg/g.
11 . The pharmaceutical composition of claim 1 , wherein the foam or hydrogel is crosslinked.
12 . A method of treating an inflammatory disease or condition in a subject in need thereof, comprising administering a therapeutically effective amount of carbon monoxide gas to the subject, wherein the carbon monoxide gas is administered using a pharmaceutical composition according to claim 1 .
13 . The method of claim 12 , wherein the pharmaceutical carrier is a foam.
14 . The method of claim 12 , wherein the pharmaceutical carrier is a solid.
15 . The method of claim 12 , wherein the pharmaceutical carrier is a hydrogel.
16 . The method of claim 12 , wherein the pharmaceutical composition is administered orally.
17 . The method of claim 12 , wherein the pharmaceutical composition is administered rectally.
18 . The method of claim 12 , wherein the inflammatory disease or condition is a gastrointestinal inflammatory disease or condition.
19 . The method of claim 12 , wherein the gastrointestinal inflammatory disease is ulcerative colitis or inflammatory bowel disease.
20 . The method of claim 12 , wherein the method further comprises co-administration of an additional anti-inflammatory agent.
21 . The method of claim 12 , wherein the method further comprises administering hydrogen sulfide or nitric oxide that has been entrapped in the gas pockets of the pharmaceutical carrier.
22 . A method of making a foam or hydrogel pharmaceutical composition according to claim 1 comprising a pharmaceutical carrier comprising gas pockets containing carbon monoxide gas, comprising the steps of:
a) dissolving xanthan gum, methylcellulose, maltodextrin, and optionally alginate into an aqueous solution to form a carrier solution;
b) heating the carrier solution to boiling;
c) cooling the carrier solution to about room temperature;
d) injecting carbon monoxide gas into the carrier solution to form a foam; and
e) optionally crosslinking with the alginate to form a hydrogel.
23 . The method of claim 22 , wherein the pharmaceutical composition is a foam.
24 . The method of claim 22 , wherein the carbon monoxide gas is injected using a whipping siphon.
25 . The method of claim 22 , wherein the carbon monoxide gas is injected at a pressure ranging from 100 psi to 400 psi.