1-32. (canceled)
33. A digital computer comprising:
a log information storage unit that stores log information, the log information being information on performance executed by a plurality of applications configured to handle image data, the information on performance corresponding to a recorded level which can be set according to each of the plurality of applications;
a network communication unit that communicates with an external device connected to a network;
a receiving unit that receives data written in eXtensible Markup Language, as a transmission request of the log information stored in the log information storage unit from the external device, through the network communication unit based on SOAP; and
a transmission unit tht generates data describing a result of the transmission request in the eXtensible Markup Language corresponding to the recording level. and transmits the data generated to the external device based on the SOAP.
34. The digital computer according to claim 33, wherein the transmitting unit generates dara including information on certification and restriction of use or information on charging, and transmits the data generated to the external device based on the SOAP.
35. The digital computer according to claim 33, wherein the receiving unit is a SOAP listener and the transmitting unit is a SOAP proxy.
36. The digital computer according to claim 33, wherein the recording level can be set according th contents of performance of an application.
37. The digital computer according to claim 33, wherein the recording level can be set according to selection of an application.
38. The digital computer according to claim 33, wherein the recording level can be set according to a mode performance of an application.
39. The digital computer according to claim 33, further comprising a recording level setting unit being capable of setting the recording level.
40. An external device comprising:
a network communication unit that communicates with a digital computer connected to a network, the digital computer including a log information storage unit that stores log information, the log information being information on performance executed by a plurality of application which are capable of handeling image data, the information on performance corresponding to a recording level which can be set according to each of the plurality of applications;
a transmitting unit that generates data in the eXtensible Markup Language corresponding to the recording level, and transmits the data generated to the digital computer based on SOAP; and
a receiving unit that receives data written in eXtensible Markup Language. as a result of transmission request from the digital computer, based on the SOAP.
41. The external device according to claim 40, wherein the receiving unit is a SOAP listener and the transmitting unit is a SOAP proxy.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A method for treating a patient who has an immunoinflammatory disorder or is at risk for developing an immunoinflammatory disorder, said method comprising administering to said patient:
(a) a corticosteroid; and
(b) a compound having the formula:
6
wherein each Z and each Z is, independently, N, O, C,
7
wherein when Z or Z is O or
8
then p1,
when Z or Z is N,
9
then p2,
when Z or Z is C, then p3;
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, CnY2n1, wherein
n3-7 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-dibenzylaminopyrimido5,4-dpyrimidine.
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-bisN,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 algestone, 6-alpha-fluoroprednisolone, 6-alpha-methylprednisolone, 6-alpha-methylprednisolone 21-acetate, 6-alpha-methylprednisolone 21-hemisuccinate sodium salt, 6-alpha,9-alpha-difluoroprednisolone 21-acetate 17-butyrate, amcinafal, beclomethasone, beclomethasone dipropionate, beclomethasone dipropionate monohydrate, 6-beta-hydroxycortisol, betamethasone, betamethasone-17-valerate, budesonide, clobetasol, clobetasol propionate, clobetasone, clocortolone, clocortolone pivalate, cortisone, cortisone acetate, cortodoxone, deflazacort, 21-deoxycortisol, deprodone, descinolone, desonide, desoximethasone, dexamethasone, dexamethasone-21-acetate, dichlorisone, diflorasone, diflorasone diacetate, diflucortolone, doxibetasol, fludrocortisone, flumethasone, flumethasone pivalate, flumoxonide, flunisolide, fluocinonide, fluocinolone acetonide, 9-fluorocortisone, fluorohydroxyandrostenedione, fluorometholone, fluorometholone acetate, fluoxymesterone, flupredidene, fluprednisolone, flurandrenolide, formocortal, halcinonide, halometasone, halopredone, hyrcanoside, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cypionate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone probutate, hydrocortisone valerate, 6-hydroxydexamethasone, isoflupredone, isoflupredone acetate, isoprednidene, meclorisone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, paramethasone, paramethasone acetate, prednisolone, prednisolone acetate, prednisolone metasulphobenzoate, prednisolone sodium phosphate, prednisolone tebutate, prednisolone-21-hemisuccinate free acid, prednisolone-21-acetate, prednisolone-21 (beta-D-glucuronide), prednisone, prednylidene, procinonide, tralonide, triamcinolone, triamcinolone acetonide, triamcinolone acetonide 21-palmitate, triamcinolone diacetate, triamcinolone hexacetonide, or wortmannin.
6. The method of claim 5, wherein said corticosteroid is fludrocortisone or prednisolone.
7. The method of claim 6, wherein said compound is dipyridamole.
8. The method of claim 1, wherein said compound and said corticosteroid are administered within ten days of each other.
9. The method of claim 8, wherein said compound and said corticosteroid are administered within five days of each other.
10. The method of claim 9, wherein said compound and said corticosteroid are administered within twenty-four hours of each other.
11. The method of claim 10, wherein said compound and said corticosteroid are administered simultaneously.
12. The method of claim 11, wherein said compound and said corticosteroid are administered in the same pharmaceutical formulation.
13. The method of claim 1, wherein said immunoinflammatory disorder is rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn’s disease, inflammatory dermatosis, or stroke induced brain cell death.
14. The method of claim 1, wherein said compound is administered in an amount of 0.5-800 mgday, and said corticosteroid is administered in an amount of 0.1-1500 mgday.
15. The method of claim 14, wherein said compound is administered in an amount of 18-600 mgday, and said corticosteroid is administered in an amount of 0.5-30 mgday.
16. The method of claim 15, wherein said corticosteroid is administered in an amount of 0.5-10 mgday.
17. A pharmaceutical composition comprising
(i) a corticosteroid;
(ii) a compound having the formula:
10
wherein each Z and each Z is, independently, N, O, C,
11
wherein when Z or Z is O or
12
then p1,
when Z or Z is N,
13
then p2,
when Z or Z is C, then p3;
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, CnY2n1, wherein
n3-7 inclusively; and
each Y is independently: H, F, Cl, Br, or I; and
(iii) a pharmaceutically acceptable excipient.
18. The composition of claim 17, wherein said compound is a 2,6-disubstituted 4,8-dibenzylaminopyrimido5,4-dpyrimidine.
19. The composition of claim 18, wherein said compound is dipyridamole, mopidamole, dipyridamole monoacetate, NU3026, NU3059, NU3060, or NU3076.
20. The composition of claim 17, wherein said corticosteroid is algestone, 6-alpha-fluoroprednisolone, 6-alpha-methylprednisolone, 6-alpha-methylprednisolone 21-acetate, 6-alpha-methylprednisolone 21-hemisuccinate sodium salt, 6-alpha,9-alpha-difluoroprednisolone 21-acetate 17-butyrate, amcinafal, beclomethasone, beclomethasone dipropionate, beclomethasone dipropionate monohydrate, 6-beta-hydroxycortisol, betamethasone, betamethasone-17-valerate, budesonide, clobetasol, clobetasol propionate, clobetasone, clocortolone, clocortolone pivalate, cortisone, cortisone acetate, cortodoxone, deflazacort, 21-deoxycortisol, deprodone, descinolone, desonide, desoximethasone, dexamethasone, dexamethasone-21-acetate, dichlorisone, diflorasone, diflorasone diacetate, diflucortolone, doxibetasol, fludrocortisone, flumethasone, flumethasone pivalate, flumoxonide, flunisolide, fluocinonide, fluocinolone acetonide, 9-fluorocortisone, fluorohydroxyandrostenedione, fluorometholone, fluorometholone acetate, fluoxymesterone, flupredidene, fluprednisolone, flurandrenolide, formocortal, halcinonide, halometasone, halopredone, hyrcanoside, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cypionate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone probutate, hydrocortisone valerate, 6-hydroxydexamethasone, isoflupredone, isoflupredone acetate, isoprednidene, meclorisone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, paramethasone, paramethasone acetate, prednisolone, prednisolone acetate, prednisolone metasulphobenzoate, prednisolone sodium phosphate, prednisolone tebutate, prednisolone-21-hemisuccinate free acid, prednisolone-21-acetate, prednisolone-21 (beta-D-glucuronide), prednisone, prednylidene, procinonide, tralonide, triamcinolone, triamcinolone acetonide, triamcinolone acetonide 21-palmitate, triamcinolone diacetate, triamcinolone hexacetonide, or wortmannin.
21. A pharmaceutical pack comprising
(i) a corticosteroid; and
(ii) a compound having the formula:
14
wherein each Z and each Z is, independently, N, O, C,
15
wherein when Z or Z is O or
16
then p1,
when Z or Z is N,
17
then p2,
when Z or Z is C, then p3;
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, CnY2n1, wherein
n3-7 inclusively; and
each Y is independently: H, F, Cl, Br, or I.
22. The pharmaceutical pack of claim 21, wherein said compound is a 2,6-disubstituted 4,8-dibenzylaminopyrimido5,4-dpyrimidine.
23. The pharmaceutical pack of claim 22, wherein said compound is dipyridamole, mopidamole, dipyridamole monoacetate, NU3026, NU3059, NU3060, or NU3076.
24. The pharmaceutical pack of claim 23, wherein said compound is dipyridamole.
25. The pharmaceutical pack of claim 21, wherein said corticosteroid is algestone, 6-alpha-fluoroprednisolone, 6-alpha-methylprednisolone, 6-alpha-methylprednisolone 21-acetate, 6-alpha-methylprednisolone 21-hemisuccinate sodium salt, 6-alpha,9-alpha-difluoroprednisolone 21-acetate 17-butyrate, amcinafal, beclomethasone, beclomethasone dipropionate, beclomethasone dipropionate monohydrate, 6-beta-hydroxycortisol, betamethasone, betamethasone-17-valerate, budesonide, clobetasol, clobetasol propionate, clobetasone, clocortolone, clocortolone pivalate, cortisone, cortisone acetate, cortodoxone, deflazacort, 21-deoxycortisol, deprodone, descinolone, desonide, desoximethasone, dexamethasone, dexamethasone-21-acetate, dichlorisone, diflorasone, diflorasone diacetate, diflucortolone, doxibetasol, fludrocortisone, flumethasone, flumethasone pivalate, flumoxonide, flunisolide, fluocinonide, fluocinolone acetonide, 9-fluorocortisone, fluorohydroxyandrostenedione, fluorometholone, fluorometholone acetate, fluoxymesterone, flupredidene, fluprednisolone, flurandrenolide, formocortal, halcinonide, halometasone, halopredone, hyrcanoside, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cypionate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone probutate, hydrocortisone valerate, 6-hydroxydexamethasone, isoflupredone, isoflupredone acetate, isoprednidene, meclorisone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, paramethasone, paramethasone acetate, prednisolone, prednisolone acetate, prednisolone metasulphobenzoate, prednisolone sodium phosphate, prednisolone tebutate, prednisolone-21-hemisuccinate free acid, prednisolone-21-acetate, prednisolone-21(beta-D-glucuronide), prednisone, prednylidene, procinonide, tralonide, triamcinolone, triamcinolone acetonide, triamcinolone acetonide 21-palmitate, triamcinolone diacetate, triamcinolone hexacetonide, or wortmannin.
26. The pharmaceutical pack of claim 21, wherein said compound and said corticosteroid are formulated separately and in individual dosage amounts.
27. The pharmaceutical pack of claim 21, wherein said compound and said corticosteroid are formulated together and in individual dosage amounts.
28. A method for treating a patient who has an immunoinflammatory disorder or is at risk for developing an immunoinflammatory disorder, said method comprising administering to said patient:
(a) two or more corticosteroids; and
(b) a compound having the formula:
18
wherein each Z and each Z is, independently, N, O, C,
19
wherein when Z or Z is O or
20
then p1,
when Z or Z is N,
21
then p2,
when Z or Z is C, then p3;
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, CnY2n1, wherein
n3-7 inclusively; and
each Y is independently: H, F, Cl, Br, or I;
wherein each of said compound and said two or more corticosteroids are administered in amounts sufficient to treat said patient.
29. The method of claim 28, wherein said compound is dipyridamole, mopidamole, dipyridamole monoacetate, NU3026, NU3059, NU3060, or NU3076.
30. The method of claim 29, wherein said compound is dipyridamole.
31. The method of claim 28, wherein at least one of said corticosteroids is algestone, 6-alpha-fluoroprednisolone, 6-alpha-methylprednisolone, 6-alpha-methylprednisolone 21-acetate, 6-alpha-methylprednisolone 21-hemisuccinate sodium salt, 6-alpha,9-alpha-difluoroprednisolone 21-acetate 17-butyrate, amcinafal, beclomethasone, beclomethasone dipropionate, beclomethasone dipropionate monohydrate, 6-beta-hydroxycortisol, betamethasone, betamethasone-17-valerate, budesonide, clobetasol, clobetasol propionate, clobetasone, clocortolone, clocortolone pivalate, cortisone, cortisone acetate, cortodoxone, deflazacort, 21-deoxycortisol, deprodone, descinolone, desonide, desoximethasone, dexamethasone, dexamethasone-21-acetate, dichlorisone, diflorasone, diflorasone diacetate, diflucortolone, doxibetasol, fludrocortisone, flumethasone, flumethasone pivalate, flumoxonide, flunisolide, fluocinonide, fluocinolone acetonide, 9-fluorocortisone, fluorohydroxyandrostenedione, fluorometholone, fluorometholone acetate, fluoxymesterone, flupredidene, fluprednisolone, flurandrenolide, formocortal, halcinonide, halometasone, halopredone, hyrcanoside, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cypionate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone probutate, hydrocortisone valerate, 6-hydroxydexamethasone, isoflupredone, isoflupredone acetate, isoprednidene, meclorisone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, paramethasone, paramethasone acetate, prednisolone, prednisolone acetate, prednisolone metasulphobenzoate, prednisolone sodium phosphate, prednisolone tebutate, prednisolone-21-hemisuccinate free acid, prednisolone-21-acetate, prednisolone-21(beta-D-glucuronide), prednisone, prednylidene, procinonide, tralonide, triamcinolone, triamcinolone acetonide, triamcinolone acetonide 21-palmitate, triamcinolone diacetate, triamcinolone hexacetonide, or wortmannin.
32. A method for identifying combinations of compounds useful for treating a patient having an immunoinflammatory disorder, said method comprising the steps of:
(a) contacting immune cells in vitro with (i) a first compound selected from the group consisting of dipyridamole, fludrocortisone, and prednisolone, and (ii) a candidate compound; and
(b) determining whether the combination of said first compound and said candidate compound reduces TNF levels in said immune cells relative to immune cells contacted with said first compound but not contacted with said candidate compound, or peripheral blood mononuclear cells contacted with said candidate compound but not with said first compound, wherein a reduction of said TNF levels identifies said combination as a combination that is useful for treating a patient having an immunoinflammatory disorder.
33. A method for suppressing the production of one or more proinflammatory cytokines in a patient in need thereof, said method comprising administering to the patient a cytokine suppressing amount of the pharmaceutical composition of claim 17.
34. The method of claim 33, wherein one of said cytokines is TNF.
35. A kit comprising (i) the pharmaceutical pack of claim 21 and (ii) instructions for administering said pack to a patient diagnosed with or at risk for developing an immunoinflammatory disorder.
36. A method for treating a patient who has an immunoinflammatory disorder or is at risk for developing an immunoinflammatory disorder, said method comprising administering to said patient (i) dipyridimole and (ii) prednisolone or fludricortisone within one hour of each other in amounts and for a duration sufficient to treat said patient.