Therapeutic delivery of carbon monoxide

1 . A pharmaceutical preparation, comprising a metal carbonyl compound or pharmaceutically acceptable salt thereof, a guanylate cyclase stimulant or stabilizer and at least one pharmaceutically acceptable carrier.

2 . A pharmaceutical preparation according to claim 1 , wherein the metal carbonyl makes available CO suitable for physiological effect, for delivery of carbon monoxide to a physiological target.

3 . A pharmaceutical preparation according to claim 2 , wherein said metal carbonyl compound makes CO available by at least one of the following means:

1) CO derived by dissociation of the metal carbonyl is present in the composition in dissolved form;

2) on contact with a solvent or ligand the metal carbonyl releases CO;

3) on contact with a tissue, organ or cell the metal carbonyl releases CO;

4) on irradiation the metal carbonyl releases CO.

4 . A pharmaceutical preparation according to claim 1 , wherein said metal carbonyl compound and said guanylate cyclase stimulant/stabilizer are combined in a single composition.

5 . A pharmaceutical preparation according to claim 1 , wherein said metal carbonyl compound and said guanylate cyclase stabilizer/stimulant are in separate compositions for administration simultaneously or sequentially.

6 . A pharmaceutical preparation according to claim 1 wherein the metal carbonyl compound has the formula M(CO) x A y where x is at least one, y is at least one, M is a metal, the or each A is an atom or group bonded to M by an ionic, covalent or coordination bond but is not CO, and in the case where y>1 each A may be the same or different, or a pharmaceutically acceptable salt of such a compound.

7 . A pharmaceutical preparation according to claim 6 , wherein M is a transition metal.

8 . A pharmaceutical preparation according to claim 6 wherein A is selected from neutral or anionic ligands, such as halide, or derived from Lewis bases and having N, P, O, S or C as the coordinating atom(s).

9 . A pharmaceutical preparation according to any one of claim 1 , wherein the metal carbonyl compound has the formula

M(CO) x A y B z

where

M is Fe, Co or Ru,

x is at least one,

y is at least one,

z is zero or at least one,

each A is a ligand other than CO and is monodentate or polydentate with respect to M and is selected from the amino acids

alanine

arginine

asparagine

aspartic acid

cysteine

glutamic acid

glutamine

glycine

histidine

isoleucine

leucine

lysine

methionine

phenylalanine

proline

serine

threonine

tryptophan

tyrosine

valine

[O(CH 2 COO) 2 ] 2− and

[NH(CH 2 COO) 2 ] 2− , and

B is optional and is a ligand other than CO.

10 . A pharmaceutical preparation according to claim, 1 wherein the guanylate cyclase stimulant/stabilizer is YC-1.

11 . A pharmaceutical composition according to claim 1 , adapted for delivery by an oral, intravenous, subcutaneous, nasal, inhalatory, intramuscular, intraperitoneal or suppository route.

12 . A method of introducing a therapeutic agent to a mammal comprising the step of administering a pharmaceutical preparation according to any one of claim 1 .

13 . A method of introducing a therapeutic agent to a mammal comprising:

a) administering a metal carbonyl; and

b) administering a guanylate cyclase stimulant or stabiliser.

14 . A method according to claim 13 , wherein the metal carbonyl makes CO available for physiological effect, for delivery of CO to a physiological target.

15 . A method according to claim 14 , wherein said metal carbonyl compound makes CO available by at least one of the following means:

1 ) CO derived by dissociation of the metal carbonyl is present in the composition in dissolved form;

2 ) on contact with a solvent or ligand the metal carbonyl releases CO;

3 ) on contact with a tissue, organ or cell the metal carbonyl releases CO;

4 ) on irradiation the metal carbonyl releases CO.

16 - 22 . (canceled)

23 . A method according to claim 15 , wherein the metal carbonyl compound and/or the guanylate cyclase stabilizer/stimulant is administered by an oral, intravenous, subcutaneous, nasal, inhalatory, intramuscular, intraperitoneal or suppository route.

24 . A method according to claim 12 , wherein the metal carbonyl and guanylate cyclase stimulant/stabilizer are administered to an extracorporeal body organ.

25 . A method according to claim 12 , where the administration is for the stimulation of vasodilation, or for treatment of any of hypertension, such as acute, pulmonary and chronic hypertension, radiation damage, endotoxic shock, inflammation, inflammatory-related diseases such as asthma and rheumatoid arthritis, hyperoxia-induced injury, apoptosis, cancer, transplant rejection, arteriosclerosis, post-ischemic organ damage, myocardial infarction, angina, haemorrhagic shock, sepsis, penile erectile dysfunction, adult respiratory distress syndrome and inhibition of platelet aggregation.

26 . A kit for medical treatment comprising a) a metal carbonyl compound; and b) a guanylate cyclase stimulant/stabilizer.

27 . A kit according to claim 26 , wherein the metal carbonyl is capable of making available CO suitable for physiological effect.

28 - 35 . (canceled)