Methods and reagents for the treatment of immunoinflammatory disorders

• US 20070010502A1
• Filed: 09/07/2006
• Published: 01/11/2007
• Est. Priority Date: 10/15/2003
• Status: Active Grant

• Current Assignee: Zalicus Inc. (EPIRUS Biopharmaceuticals, Inc.)
• Original Assignee: CombinatoRx, Inc. (EPIRUS Biopharmaceuticals, Inc.)
• Inventors: Manivasakam, Palaniyandi, Keith, Curtis, Zimmermann, Grant, Borisy, Alexis, Smith, Brendan, Foley, Michael, Hurst, Nicole, Jost-Price, Edward, Auspitz, Benjamin, Slavonic, Michael
• Granted Patent: US 8,080,553 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The invention features a method for treating a patient diagnosed with, or at risk of developing, an immunoinflammatory disorder by administering to the patient a tetra-substituted pyrimidopyrimidine, either alone or in combination with one or more additional agents. The invention also features a composition containing a tetra-substituted pyrimidopyrimidine in combination with one or more additional agents.

Claims

1. A method for treating a patient who has an immunoinflammatory disorder or is at risk for developing an immunoinflammatory disorder, said immunoinflammatory disorder selected from the group consisting of acne vulgaris;

acute respiratory distress syndrome;

Addison'"'"'s disease;

allergic rhinitis;

allergic intraocular inflammatory diseases;

ANCA-associated small-vessel vasculitis;

arthritis, asthma;

atherosclerosis;

atopic dermatitis;

autoimmune hemolytic anemia;

autoimmune hepatitis;

Behcet'"'"'s disease;

Bell'"'"'s palsy;

bullous pemphigoid;

cerebral ischaemia;

chronic obstructive pulmonary disease;

cirrhosis;

Cogan'"'"'s syndrome;

contact dermatitis;

COPD;

Cushing'"'"'s syndrome;

dermatomyositis;

discoid lupus erythematosus;

eosinophilic fasciitis;

erythema nodosum;

exfoliative dermatitis;

focal glomerulosclerosis;

giant cell arteritis;

gout;

gouty arthritis;

graft-versus-host disease;

hand eczema;

Henoch-Schonlein purpura;

herpes gestationis;

hirsutism;

idiopathic cerato-scleritis;

idiopathic pulmonary fibrosis;

idiopathic thrombocytopenic purpura;

inflammatory bowel or gastrointestinal disorders, lichen planus;

lupus nephritis;

lymphomatous tracheobronchitis;

macular edema;

myasthenia gravis;

myositis;

osteoarthritis;

pancreatitis;

pemphigoid gestationis;

pemphigus vulgaris;

polyarteritis nodosa;

polymyalgia rheumatica;

pruritus scroti;

pruritis/inflammation, psoriatic arthritis;

relapsing polychondritis;

rosacea;

sarcoidosis;

segmental glomerulosclerosis;

septic shock syndrome;

shoulder tendinitis or bursitis;

Still'"'"'s disease;

Sweet'"'"'s disease;

Takayasu'"'"'s arteritis;

temporal arteritis;

toxic epidermal necrolysis;

tuberculosis;

uveitis;

vasculitis; and

Wegener'"'"'s granulomatosis;

said method comprising administering to said patient;

(a) a corticosteroid; and

(b) a compound having the formula;

wherein each Z and each Z′

is, independently, N, O, C,

wherein when Z or Z′

is O or

then p=1,

when Z or Z′

is N,

then p=2,

when Z or Z′

is C, then p=3;

each R₁ is, independently, X, OH, N-alkyl, a branched or unbranched alkyl group having 1 to 20 carbon atoms, a heterocycle, or, when p>

1, two R₁ groups from a common Z or Z′

atom, in combination with each other, represent —

(CY₂)_k—

, wherein k is an integer between 4 and 6, inclusive;

each X is, independently, Y, CY₃, C(CY₃)₃, CY₂CY₃, (CY₂)_1-5OY, C_nY_2n-1, wherein n=3-7 inclusively; and

each Y is independently;

H, F, Cl, Br, or I, wherein said compound and said corticosteroid are administered simultaneously or within 14 days of each other, in amounts and for a duration sufficient to treat said patient.

2. The method of claim 1, wherein said compound is a 2,6-disubstituted 4,8-dibenzylaminopyrimido[5,4-d]pyrimidine.

3. The method of claim 1, wherein said compound is dipyridamole, mopidamole, dipyridamole monoacetate, NU3026 (2,6-di-(2,2-dimethyl-1,3-dioxolan-4-yl)-methoxy-4,8-di-piperidinopyrimidopyrimidine), NU3059 (2,6-bis-(2,3-dimethyoxypropoxy)-4,8-di-piperidinopyrimidopyrimidine), NU3060 (2,6-bis[N,N-di(2-methoxy)ethyl]-4,6-di-piperidinopyrimidopyrimidine), or NU3076 (2,6-bis(diethanolamino)-4,8-di-4-methoxybenzylaminopyrimidopyrimidine).

4. The method of claim 3, wherein said compound is dipyridamole.

5. The method of claim 1, wherein said corticosteroid is 11-alpha, 17-alpha,21-trihydroxypregn-4-ene-3,20-dione;

11-beta,16-alpha,17,21-tetrahydroxypregn-4-ene-3,20-dione;

11-beta,16-alpha,17,21-tetrahydroxypregn-1,4-diene-3,20-dione;

11-beta,17-alpha,21-trihydroxy-6-alpha-methylpregn-4-ene-3,20-dione;

11-dehydrocorticosterone;

11-deoxycortisol;

11-hydroxy-1,4-androstadiene-3,17-dione;

11-ketotestosterone;

14-hydroxyandrost-4-ene-3,6,17-trione;

15,17-dihydroxyprogesterone;

16-methylhydrocortisone;

17,21-dihydroxy-16-alpha-methylpregna-1,4,9(11)-triene-3,20-dione;

17-alpha-hydroxypregn-4-ene-3,20-dione;

17-alpha-hydroxypregnenolone;

17-hydroxy-16-beta-methyl-5-beta-pregn-9(11)-ene-3,20-dione;

17-hydroxy-4,6,8(14)-pregnatriene-3,20-dione;

17-hydroxypregna-4,9(11)-diene-3,20-dione;

18-hydroxycorticosterone;

18-hydroxycortisone;

1 8-oxocortisol;

21-deoxyaldosterone;

21-deoxycortisone;

2-deoxyecdysone;

2-methylcortisone;

3-dehydroecdysone;

4-pregnene-17-alpha,20-beta, 21-triol-3,11-dione;

6,17,20-trihydroxypregn-4-ene-3-one;

6-alpha-hydroxycortisol;

6-alpha-fluoroprednisolone, 6-alpha-methylprednisolone, 6-alpha-methylprednisolone 21-acetate, 6-alpha-methylprednisolone 21-hemisuccinate sodium salt, 6-beta-hydroxycortisol, 6-alpha, 9-alpha-difluoroprednisolone 21-acetate 17-butyrate, 6-hydroxycorticosterone;

6-hydroxydexamethasone;

6-hydroxyprednisolone;

9-fluorocortisone;

alclometasone dipropionate;

aldosterone;

algestone;

alphaderm;

amadinone;

amcinonide;

anagestone; and

rostenedione;

anecortave acetate;

beclomethasone;

beclomethasone dipropionate;

beclomethasone dipropionate monohydrate;

betamethasone 17-valerate;

betamethasone sodium acetate;

betamethasone sodium phosphate;

betamethasone valerate;

bolasterone;

budesonide;

calusterone;

chlormadinone;

chloroprednisone;

chloroprednisone acetate;

cholesterol;

clobetasol;

clobetasol propionate;

clobetasone;

clocortolone;

clocortolone pivalate;

clogestone;

cloprednol;

corticosterone;

cortisol;

cortisol acetate;

cortisol butyrate;

cortisol cypionate;

cortisol octanoate;

cortisol sodium phosphate;

cortisol sodium succinate;

cortisol valerate;

cortisone;

cortisone acetate;

cortodoxone;

daturaolone;

deflazacort, 21-deoxycortisol, dehydroepiandrosterone;

delmadinone;

deoxycorticosterone;

deprodone;

descinolone;

desonide;

desoximethasone;

dexafen;

dexamethasone;

dexamethasone 21-acetate;

dexamethasone acetate;

dexamethasone sodium phosphate;

dichlorisone;

diflorasone;

diflorasone diacetate;

diflucortolone;

dihydroelatericin a;

domoprednate;

doxibetasol;

ecdysone;

ecdysterone;

endrysone;

enoxolone;

flucinolone;

fludrocortisone;

fludrocortisone acetate;

flugestone;

flumethasone;

flumethasone pivalate;

flumoxonide;

flunisolide;

fluocinolone;

fluocinolone acetonide;

fluocinonide;

9-fluorocortisone;

fluocortolone;

fluorohydroxyandrostenedione;

fluorometholone;

fluorometholone acetate;

fluoxymesterone;

fluprednidene;

fluprednisolone;

flurandrenolide;

fluticasone;

fluticasone propionate;

formebolone;

formestane;

formocortal;

gestonorone;

glyderinine;

halcinonide;

hyrcanoside;

halometasone;

halopredone;

haloprogesterone;

hydrocortisone;

hydrocortisone 21-butyrate;

hydrocortisone aceponate;

hydrocortisone acetate;

hydrocortisone buteprate;

hydrocortisone butyrate;

hydrocortisone cypionate;

hydrocortisone hemisuccinate;

hydrocortisone probutate;

hydrocortisone sodium phosphate;

hydrocortisone sodium succinate;

hydrocortisone valerate;

hydroxyprogesterone;

inokosterone;

isoflupredone;

isoflupredone acetate;

isoprednidene;

meclorisone;

mecortolon;

medrogestone;

medroxyprogesterone;

medrysone;

megestrol;

megestrol acetate;

melengestrol;

meprednisone;

methandrostenolone;

methylprednisolone;

methylprednisolone aceponate;

methylprednisolone acetate;

methylprednisolone hemisuccinate;

methylprednisolone sodium succinate;

methyltestosterone;

metribolone;

mometasone;

mometasone furoate;

mometasone furoate monohydrate;

nisone;

nomegestrol;

norgestomet;

norvinisterone;

oxymesterone;

paramethasone;

paramethasone acetate;

ponasterone;

prednisolamate;

prednisolone;

prednisolone 21-hemisuccinate;

prednisolone acetate;

prednisolone farnesylate;

prednisolone hemisuccinate;

prednisolone-21 (beta-D-glucuronide);

prednisolone metasulphobenzoate;

prednisolone sodium phosphate;

prednisolone steaglate;

prednisolone tebutate;

prednisolone tetrahydrophthalate;

prednisone;

prednival;

prednylidene;

pregnenolone;

procinonide;

tralonide;

progesterone;

promegestone;

rhapontisterone;

rimexolone;

roxibolone;

rubrosterone;

stizophyllin;

tixocortol;

topterone;

triamcinolone;

triamcinolone acetonide;

triamcinolone acetonide 21-palmitate;

triamcinolone diacetate;

triamcinolone hexacetonide;

trimegestone;

turkesterone;

or wortmannin.

6. The method of claim 5, wherein said corticosteroid is fludrocortisone, prednisone, or prednisolone.

7. The method of claim 6, wherein said compound is dipyridamole.

8. The method of claim 7, wherein said dipyridamole is administered systemically.

9. The method of claim 8, wherein said dipyridamole is administered orally or intravenously.

10. The method of claim 1, wherein said compound and said corticosteroid are administered within ten days of each other.

11. The method of claim 10, wherein said compound and said corticosteroid are administered within five days of each other.

12. The method of claim 11, wherein said compound and said corticosteroid are administered within twenty-four hours of each other.

13. The method of claim 12, wherein said compound and said corticosteroid are administered simultaneously.

14. The method of claim 13, wherein said compound and said corticosteroid are administered in the same pharmaceutical formulation.

15. The method of claim 1, wherein said immunoinflammatory disorder is osteoarthritis.

16. A method for treating a patient who has an immunoinflammatory disorder or is at risk for developing an immunoinflammatory disorder, said immunoinflammatory disorder selected from the group consisting of acne vulgaris;

acute respiratory distress syndrome;

Addison'"'"'s disease;

allergic rhinitis;

allergic intraocular inflammatory diseases;

ANCA-associated small-vessel vasculitis;

arthritis, asthma;

atherosclerosis;

atopic dermatitis;

autoimmune hemolytic anemia;

autoimmune hepatitis;

Behcet'"'"'s disease;

Bell'"'"'s palsy;

bullous pemphigoid;

cerebral ischaemia;

chronic obstructive pulmonary disease;

cirrhosis;

Cogan'"'"'s syndrome;

contact dermatitis;

COPD;

Cushing'"'"'s syndrome;

dermatomyositis;

discoid lupus erythematosus;

eosinophilic fasciitis;

erythema nodosum;

exfoliative dermatitis;

focal glomerulosclerosis;

giant cell arteritis;

gout;

gouty arthritis;

graft-versus-host disease;

hand eczema;

Henoch-Schonlein purpura;

herpes gestationis;

hirsutism;

idiopathic cerato-scleritis;

idiopathic pulmonary fibrosis;

idiopathic thrombocytopenic purpura;

inflammatory bowel or gastrointestinal disorders, lichen planus;

lupus nephritis;

lymphomatous tracheobronchitis;

macular edema;

myasthenia gravis;

myositis;

osteoarthritis;

pancreatitis;

pemphigoid gestationis;

pemphigus vulgaris;

polyarteritis nodosa;

polymyalgia rheumatica;

pruritus scroti;

pruritis/inflammation, psoriatic arthritis;

relapsing polychondritis;

rosacea;

sarcoidosis;

segmental glomerulosclerosis;

septic shock syndrome;

shoulder tendinitis or bursitis;

Still'"'"'s disease;

Sweet'"'"'s disease;

Takayasu'"'"'s arteritis;

temporal arteritis;

toxic epidermal necrolysis;

tuberculosis;

uveitis;

vasculitis; and

Wegener'"'"'s granulomatosis;

said method comprising administering to said patient a composition comprising;

(a) a corticosteroid; and

(b) a compound having the formula;

wherein each Z and each Z′

is, independently, N, O, C,

wherein when Z or Z′

is O or

then p=1,

when Z or Z′

is N,

then p=2,

when Z or Z′

is C, then p=3;

each R₁ is, independently, X, OH, N-alkyl, a branched or unbranched alkyl group having 1 to 20 carbon atoms, a heterocycle, or, when p>

1, two R₁ groups from a common Z or Z′

atom, in combination with each other, represent —

CY₂)_k—

, wherein k is an integer between 4 and 6, inclusive;

each X is, independently, Y, CY₃, C(CY₃)₃, CY₂CY₃, (CY₂)_1-5OY, C_nY_2n-1, wherein n=3-7 inclusively; and

each Y is independently;

H, F, Cl, Br, or I, in an amount and for a duration sufficient to treat said patient.

17. The method of claim 16, wherein said compound is dipyridamole, mopidamole, dipyridamole monoacetate, NU3026 (2,6-di-(2,2-dimethyl-1,3-dioxolan-4-yl)-methoxy-4,8-di-piperidinopyrimidopyrimidine), NU3059 (2,6-bis-(2,3-dimethyoxypropoxy)-4,8-di-piperidinopyrimidopyrimidine), NU3060 (2,6-bis[N,N-di(2-methoxy)ethyl]-4,6-di-piperidinopyrimidopyrimidine), or NU3076 (2,6-bis(diethanolamino)-4,8-di-4-methoxybenzylaminopyrimidopyrimidine).

18. The method of claim 17, wherein said compound is dipyridamole.

19. The method of claim 16, wherein said corticosteroid is 11-alpha,17-alpha,21-trihydroxypregn-4-ene-3,20-dione;

11-beta,16-alpha,17,21-tetrahydroxypregn-4-ene-3,20-dione;

11-beta,16-alpha,17,21-tetrahydroxypregn-1,4-diene-3,20-dione;

11-beta,17-alpha,21-trihydroxy-6-alpha-methylpregn-4-ene-3,20-dione;

11-dehydrocorticosterone;

11-deoxycortisol;

11-hydroxy-1,4-androstadiene-3,17-dione;

11-ketotestosterone;

14-hydroxyandrost-4-ene-3,6,17-trione;

15,17-dihydroxyprogesterone;

16-methylhydrocortisone;

17,21-dihydroxy-16-alpha-methylpregna-1,4,9(11)-triene-3,20-dione;

17-alpha-hydroxypregn-4-ene-3,20-dione;

17-alpha-hydroxypregnenolone;

17-hydroxy-16-beta-methyl-5-beta-pregn-9(11)-ene-3,20-dione;

17-hydroxy-4,6,8(14)-pregnatriene-3,20-dione;

17-hydroxypregna-4,9(11)-diene-3,20-dione;

18-hydroxycorticosterone;

18-hydroxycortisone;

18-oxocortisol;

21-deoxyaldosterone;

21-deoxycortisone;

2-deoxyecdysone;

2-methylcortisone;

3-dehydroecdysone;

4-pregnene-17-alpha,20-beta,21-triol-3,11-dione;

6,17,20-trihydroxypregn-4-ene-3-one;

6-alpha-hydroxycortisol;

6-alpha-fluoroprednisolone, 6-alpha-methylprednisolone, 6-alpha-methylprednisolone 21-acetate, 6-alpha-methylprednisolone 21-hemisuccinate sodium salt, 6-beta-hydroxycortisol, 6-alpha, 9-alpha-difluoroprednisolone 21-acetate 17-butyrate, 6-hydroxycorticosterone;

6-hydroxydexamethasone;

6-hydroxyprednisolone;

9-fluorocortisone;

alclometasone dipropionate;

aldosterone;

algestone;

alphaderm;

amadinone;

amcinonide;

anagestone; and

rostenedione;

anecortave acetate;

beclomethasone;

beclomethasone dipropionate;

beclomethasone dipropionate monohydrate;

betamethasone 17-valerate;

betamethasone sodium acetate;

betamethasone sodium phosphate;

betamethasone valerate;

bolasterone;

budesonide;

calusterone;

chlormadinone;

chloroprednisone;

chloroprednisone acetate;

cholesterol;

clobetasol;

clobetasol propionate;

clobetasone;

clocortolone;

clocortolone pivalate;

clogestone;

cloprednol;

corticosterone;

cortisol;

cortisol acetate;

cortisol butyrate;

cortisol cypionate;

cortisol octanoate;

cortisol sodium phosphate;

cortisol sodium succinate;

cortisol valerate;

cortisone;

cortisone acetate;

cortodoxone;

daturaolone;

deflazacort, 21-deoxycortisol, dehydroepiandrosterone;

delmadinone;

deoxycorticosterone;

deprodone;

descinolone;

desonide;

desoximethasone;

dexafen;

dexamethasone;

dexamethasone 21-acetate;

dexamethasone acetate;

dexamethasone sodium phosphate;

dichlorisone;

diflorasone;

diflorasone diacetate;

diflucortolone;

dihydroelatericin a;

domoprednate;

doxibetasol;

ecdysone;

ecdysterone;

endrysone;

enoxolone;

flucinolone;

fludrocortisone;

fludrocortisone acetate;

flugestone;

flumethasone;

flumethasone pivalate;

flumoxonide;

flunisolide;

fluocinolone;

fluocinolone acetonide;

fluocinonide;

9-fluorocortisone;

fluocortolone;

fluorohydroxyandrostenedione;

fluorometholone;

fluorometholone acetate;

fluoxymesterone;

fluprednidene;

fluprednisolone;

flurandrenolide;

fluticasone;

fluticasone propionate;

formebolone;

formestane;

formocortal;

gestonorone;

glyderinine;

halcinonide;

hyrcanoside;

halometasone;

halopredone;

haloprogesterone;

hydrocortisone;

hydrocortisone 21-butyrate;

hydrocortisone aceponate;

hydrocortisone acetate;

hydrocortisone buteprate;

hydrocortisone butyrate;

hydrocortisone cypionate;

hydrocortisone hemisuccinate;

hydrocortisone probutate;

hydrocortisone sodium phosphate;

hydrocortisone sodium succinate;

hydrocortisone valerate;

hydroxyprogesterone;

inokosterone;

isoflupredone;

isoflupredone acetate;

isoprednidene;

meclorisone;

mecortolon;

medrogestone;

medroxyprogesterone;

medrysone;

megestrol;

megestrol acetate;

melengestrol;

meprednisone;

methandrostenolone;

methylprednisolone;

methylprednisolone aceponate;

methylprednisolone acetate;

methylprednisolone hemisuccinate;

methylprednisolone sodium succinate;

methyltestosterone;

metribolone;

mometasone;

mometasone furoate;

mometasone furoate monohydrate;

nisone;

nomegestrol;

norgestomet;

norvinisterone;

oxymesterone;

paramethasone;

paramethasone acetate;

ponasterone;

prednisolamate;

prednisolone;

prednisolone 21-hemisuccinate;

prednisolone acetate;

prednisolone farnesylate;

prednisolone hemisuccinate;

prednisolone-21(beta-D-glucuronide);

prednisolone metasulphobenzoate;

prednisolone sodium phosphate;

prednisolone steaglate;

prednisolone tebutate;

prednisolone tetrahydrophthalate;

prednisone;

prednival;

prednylidene;

pregnenolone;

procinonide;

tralonide;

progesterone;

promegestone;

rhapontisterone;

rimexolone;

roxibolone;

rubrosterone;

stizophyllin;

tixocortol;

topterone;

triamcinolone;

triamcinolone acetonide;

triamcinolone acetonide 21-palmitate;

triamcinolone diacetate;

triamcinolone hexacetonide;

trimegestone;

turkesterone;

or wortmannin.

20. The method of claim 19, wherein said corticosteroid is fludrocortisone, prednisone, or prednisolone.

21. The method of claim 16, wherein said composition is administered systemically.

22. The method of claim 21, wherein said composition is administered orally or intravenously.

23. A method for treating a patient who has osteoarthritis said method comprising systemically administering to said patient a composition comprising dipyridamole and a corticosteroid in an amount and for a duration sufficient to treat said patient.

24. The method of claim 23, wherein said corticosteroid is fludrocortisone, prednisone, or prednisolone.

25. The method of claim 23, wherein said composition consists of active ingredients and excipients, wherein said active ingredients consist of a corticosteroid and dipyridamole.

26. The method of claim 25, wherein said corticosteroid is fludrocortisone, prednisone, or prednisolone.

27. The method of claim 26, wherein said composition is administered orally or intravenously.

28. A method for treating a patient who has an immunoinflammatory disorder or is at risk for developing an immunoinflammatory disorder, said immunoinflammatory disorder selected from the group consisting of acne vulgaris;

acute respiratory distress syndrome;

Addison'"'"'s disease;

allergic rhinitis;

allergic intraocular inflammatory diseases;

ANCA-associated small-vessel vasculitis;

arthritis, asthma;

atherosclerosis;

atopic dermatitis;

autoimmune hemolytic anemia;

autoimmune hepatitis;

Behcet'"'"'s disease;

Bell'"'"'s palsy;

bullous pemphigoid;

cerebral ischaemia;

chronic obstructive pulmonary disease;

cirrhosis;

Cogan'"'"'s syndrome;

contact dermatitis;

COPD;

Cushing'"'"'s syndrome;

dermatomyositis;

discoid lupus erythematosus;

eosinophilic fasciitis;

erythema nodosum;

exfoliative dermatitis;

focal glomerulosclerosis;

giant cell arteritis;

gout;

gouty arthritis;

graft-versus-host disease;

hand eczema;

Henoch-Schonlein purpura;

herpes gestationis;

hirsutism;

idiopathic cerato-scleritis;

idiopathic pulmonary fibrosis;

idiopathic thrombocytopenic purpura;

inflammatory bowel or gastrointestinal disorders, lichen planus;

lupus nephritis;

lymphomatous tracheobronchitis;

macular edema;

myasthenia gravis;

myositis;

osteoarthritis;

pancreatitis;

pemphigoid gestationis;

pemphigus vulgaris;

polyarteritis nodosa;

polymyalgia rheumatica;

pruritus scroti;

pruritis/inflammation, psoriatic arthritis;

relapsing polychondritis;

rosacea;

sarcoidosis;

segmental glomerulosclerosis;

septic shock syndrome;

shoulder tendinitis or bursitis;

Still'"'"'s disease;

Sweet'"'"'s disease;

Takayasu'"'"'s arteritis;

temporal arteritis;

toxic epidermal necrolysis;

tuberculosis;

uveitis;

vasculitis; and

Wegener'"'"'s granulomatosis, said method comprising administering to said patient a composition consisting of active ingredients and excipients, wherein said active ingredients consist of a corticosteroid and dipyridamole, in an amount and for a duration sufficient to treat said patient.

29. The method of claim 28, wherein said corticosteroid is fludrocortisone, prednisone, or prednisolone.

30. The method of claim 28, wherein said composition is administered systemically.

31. The method of claim 30, wherein said composition is administered orally or intravenously.