CA1078736A - Therapeutic application of 4-carbamoyl-5-hydroxyimidazole - Google Patents
Therapeutic application of 4-carbamoyl-5-hydroxyimidazoleInfo
- Publication number
- CA1078736A CA1078736A CA286,281A CA286281A CA1078736A CA 1078736 A CA1078736 A CA 1078736A CA 286281 A CA286281 A CA 286281A CA 1078736 A CA1078736 A CA 1078736A
- Authority
- CA
- Canada
- Prior art keywords
- carbamoyl
- day
- active ingredient
- hydroxyimidazole
- composition according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
NOVEL THERAPEUTIC APPLICATION OF
Abstract of the Disclosure:
4-Carbamoyl-5-hydroxyimidazole representable by the following formula:
Abstract of the Disclosure:
4-Carbamoyl-5-hydroxyimidazole representable by the following formula:
Description
` 10';~8736 The present invention relates to a novel thera-peutic application of 4-carbamoyl-5-hydroxyimidazole, which is hereinafter referred to as Compound A, and its pharma-ceutically acceptable salts.
Compound A has been known and disclosed in The Journal of the American Chemical Society, Vol. 74, p. 2892, (1952). However, its anticancer, antirheumatic and anti-nephritic properties have never been studied prior to the present invention.
As the result of an extensive study on the pharma-ceutical properties of Compound A, it has been found that Compound A has excellent anticancer, antirheumatic as well as antinephritic activities and is useful as a therapeutic agent in the treatment of cancer, rheumatism and nephritis.
In the following, the anticancer, antirheumatic and antinephritis activities and the toxicity of Compound A ;-are described.
(1) Anticancer activities.
The anticancer activities were estimated according to the methods described in "Oyo-yakuri", Vol. 4, p~ 521 (in Japanese). The results are described in Tables I and II.
. . .
iO78'736 Table I. Anticancer effects on mouse experimental tumors.
. Inhibition Ratio (%~
DosageRoute Sarcoma Ehrlich , Heptoma 180 carcinoma MH-134 ~olid) (solid) ~ (solid) ¦
_ 200 mg/kg/day x 7 i.p. 63.9 51.6 1 91.4 100 mg/kg/day x 7 i.p. 50.3 40.2 87.0 50 mg/kg/day x 7 i.p. 49.4 33.4 76.2 10100 mg/kg/day x 7 i.v. 49.6 38.8 50.0 50 mg/kg/day x 7 i.v. 42.2 34.1 41.0 200 mg/kg/day x 7 p.o. 58.9 46.4 63.6 100 mg/kg/day x 7 P-o-¦ 41-4 29.8 46.7 Table II. Anticancer effects on mouse experimental tumors.
* ) Increase in Life Span (%) DosageRoute Sarcoma Ehrlich I Heptoma 180 carcinoma , MH-134 20200 mg/kg/day x 7 ¦ i.p. >60 ~50 ~ ~75 200 mg/kg/day x 7 1 i.v. >55 >50 1 >60 200 mg/kg/day x 7 ¦ p.o. >55 >50 1 >45 Note: *) Increase in _ (Mean survival time of the Life Span treated group/Mean survival time of the control group - 1) x 100 ~.
r 1078'736 :
Compound A has been known and disclosed in The Journal of the American Chemical Society, Vol. 74, p. 2892, (1952). However, its anticancer, antirheumatic and anti-nephritic properties have never been studied prior to the present invention.
As the result of an extensive study on the pharma-ceutical properties of Compound A, it has been found that Compound A has excellent anticancer, antirheumatic as well as antinephritic activities and is useful as a therapeutic agent in the treatment of cancer, rheumatism and nephritis.
In the following, the anticancer, antirheumatic and antinephritis activities and the toxicity of Compound A ;-are described.
(1) Anticancer activities.
The anticancer activities were estimated according to the methods described in "Oyo-yakuri", Vol. 4, p~ 521 (in Japanese). The results are described in Tables I and II.
. . .
iO78'736 Table I. Anticancer effects on mouse experimental tumors.
. Inhibition Ratio (%~
DosageRoute Sarcoma Ehrlich , Heptoma 180 carcinoma MH-134 ~olid) (solid) ~ (solid) ¦
_ 200 mg/kg/day x 7 i.p. 63.9 51.6 1 91.4 100 mg/kg/day x 7 i.p. 50.3 40.2 87.0 50 mg/kg/day x 7 i.p. 49.4 33.4 76.2 10100 mg/kg/day x 7 i.v. 49.6 38.8 50.0 50 mg/kg/day x 7 i.v. 42.2 34.1 41.0 200 mg/kg/day x 7 p.o. 58.9 46.4 63.6 100 mg/kg/day x 7 P-o-¦ 41-4 29.8 46.7 Table II. Anticancer effects on mouse experimental tumors.
* ) Increase in Life Span (%) DosageRoute Sarcoma Ehrlich I Heptoma 180 carcinoma , MH-134 20200 mg/kg/day x 7 ¦ i.p. >60 ~50 ~ ~75 200 mg/kg/day x 7 1 i.v. >55 >50 1 >60 200 mg/kg/day x 7 ¦ p.o. >55 >50 1 >45 Note: *) Increase in _ (Mean survival time of the Life Span treated group/Mean survival time of the control group - 1) x 100 ~.
r 1078'736 :
(2) Antirheumatic activities.
The antirheumatic activities on adjuvant arthritis were estimated according to the methods described in "Arznei-mittel-Forschung (Drug Res.~", Vol. 22, p. 1959 (1972). The results are described in Table III.
Table III. Inhibitory effects on the adjuvant arthritis of rats. `
. ~
Dosage Route Foot Volume Inhibition Rate _ (ml1 (%) Control 2.34 _ 5 mg/kg/day x 21 ) p.o. 1.28 45.3 10 mg/kg/day x 21 )~ p.o. 0.88 62.3 25 mg/kg/day x 21 ~I P.o. 0.44 81.2 Note: *) Successive administration was performed immediately after inoculation of the adjuvant.
The antirheumatic activities on adjuvant arthritis were estimated according to the methods described in "Arznei-mittel-Forschung (Drug Res.~", Vol. 22, p. 1959 (1972). The results are described in Table III.
Table III. Inhibitory effects on the adjuvant arthritis of rats. `
. ~
Dosage Route Foot Volume Inhibition Rate _ (ml1 (%) Control 2.34 _ 5 mg/kg/day x 21 ) p.o. 1.28 45.3 10 mg/kg/day x 21 )~ p.o. 0.88 62.3 25 mg/kg/day x 21 ~I P.o. 0.44 81.2 Note: *) Successive administration was performed immediately after inoculation of the adjuvant.
(3) Antinephritic activities.
The antinephritic activities were estimated ac-cording to the methods described in "Arerugii", Vol. 24, p. 472 (1975) (in Japanese). The results are described in Table IV.
Table IV. Antinephritic effects on Masugi nephritis.
. . ..
Dosage Route Urinary Proteîn IInhibition I ~mg/24 hrs.) ~Ratio (%) . _ Cont~ol 238.9 _ 5 mg/kg/day x 16 ) p.o. 147.6 38.2 .
10 mg/kg/day x 16 ) p.o. 68.4 71.4 25 mg/kg/day x 16 ) p.o. 28.4 ¦ 88.1 r _ ...__ __ .__ ___ .
Note: *) Successive oral administration began on 2 days before the injection of nephrotoxin.
~ 30:, ; - 4 -~ . . _. . ... _ ~078736
The antinephritic activities were estimated ac-cording to the methods described in "Arerugii", Vol. 24, p. 472 (1975) (in Japanese). The results are described in Table IV.
Table IV. Antinephritic effects on Masugi nephritis.
. . ..
Dosage Route Urinary Proteîn IInhibition I ~mg/24 hrs.) ~Ratio (%) . _ Cont~ol 238.9 _ 5 mg/kg/day x 16 ) p.o. 147.6 38.2 .
10 mg/kg/day x 16 ) p.o. 68.4 71.4 25 mg/kg/day x 16 ) p.o. 28.4 ¦ 88.1 r _ ...__ __ .__ ___ .
Note: *) Successive oral administration began on 2 days before the injection of nephrotoxin.
~ 30:, ; - 4 -~ . . _. . ... _ ~078736
(4) Acute toxicity.
Acute toxicity of Compound A against mice (ICR, male, body weight 22-25 g~ was as follows.
Route LD50 p.o. greater than 2000 mg/kg i.p. greater than 500 mg/kg i.v. greater than 130 mg/kg
Acute toxicity of Compound A against mice (ICR, male, body weight 22-25 g~ was as follows.
Route LD50 p.o. greater than 2000 mg/kg i.p. greater than 500 mg/kg i.v. greater than 130 mg/kg
(5) Subacute toxicities. -" Subacute toxicities of Compound A against mice (ICR, male, body weight approximately 25 g~ were as follows.
The said compound was,orally administered for 21 days. The dosage level was 100 mg/kg/day.
~i) Body weight change Normal Food consumption Normal (ii) Haematology White blood cells (average) 6.5 x 104~mm3 Red blood cells (average) 6.0 x 106/mm3 Hemoglobin (average~ 15.1 g/dl Hematocrit value (average) 35 GOT (average) 54.4 K.U.
No adverse effect.
(ii) Urinalysis ~' Protein 30 - 100 mg/dl ,~ Glucose Negative Occult blood Negative pH 6.0 - 6.5 No adverse effect.
(iv) Autopsy No adverse effect.
; 30 (v) Relative organ weight (%) :
,' .. , , ,- - , .
~07~736 Liver (averaye~ 6.24 Kidney (averagel 1.50 Spleen ~average) ~.30 Thymus (average) 0.20 Heart (average) 0.49 Testis (average) ~.38 Lung (average~ 0.81 (vi) Clinical signs No adverse effect except slight involution of ~-spleen.
As stated above, it is evident that Compound A is an excellent therapeutic agent for cancer, rheumatism and nephritis with low toxicity. Moreover, it is an advanta-geous merit that the agent can be administered orally as well as by injection.
Compound A is active at dosage levels of 0.3 - 1.0 g per day for adult when used in therapy of rheumatism or nephritis, and of 3 - 10 g per day for adult when used in cancer therapy.
Compound A may be used in free form, or prefer-ably, in the form of a pharmaceutically acceptable addition salt thereof. Among these salts are, for example, the ~~~
hydrochloride, the sodium salt, etc.
One of the preferred routes of administration is orally, in the form of an oral dosage unit, for example a tablet or capsule. A sustained capsule is also acceptable.
These compositions are formulated in a manner well-known to pharmaceutical chemists, utilizing standard pharmaceutical excipients such as syrup, gum arabic, gelatin, sorbit, tragacanth, polyvinylpyrrolidone, lactose, glucose, corn
The said compound was,orally administered for 21 days. The dosage level was 100 mg/kg/day.
~i) Body weight change Normal Food consumption Normal (ii) Haematology White blood cells (average) 6.5 x 104~mm3 Red blood cells (average) 6.0 x 106/mm3 Hemoglobin (average~ 15.1 g/dl Hematocrit value (average) 35 GOT (average) 54.4 K.U.
No adverse effect.
(ii) Urinalysis ~' Protein 30 - 100 mg/dl ,~ Glucose Negative Occult blood Negative pH 6.0 - 6.5 No adverse effect.
(iv) Autopsy No adverse effect.
; 30 (v) Relative organ weight (%) :
,' .. , , ,- - , .
~07~736 Liver (averaye~ 6.24 Kidney (averagel 1.50 Spleen ~average) ~.30 Thymus (average) 0.20 Heart (average) 0.49 Testis (average) ~.38 Lung (average~ 0.81 (vi) Clinical signs No adverse effect except slight involution of ~-spleen.
As stated above, it is evident that Compound A is an excellent therapeutic agent for cancer, rheumatism and nephritis with low toxicity. Moreover, it is an advanta-geous merit that the agent can be administered orally as well as by injection.
Compound A is active at dosage levels of 0.3 - 1.0 g per day for adult when used in therapy of rheumatism or nephritis, and of 3 - 10 g per day for adult when used in cancer therapy.
Compound A may be used in free form, or prefer-ably, in the form of a pharmaceutically acceptable addition salt thereof. Among these salts are, for example, the ~~~
hydrochloride, the sodium salt, etc.
One of the preferred routes of administration is orally, in the form of an oral dosage unit, for example a tablet or capsule. A sustained capsule is also acceptable.
These compositions are formulated in a manner well-known to pharmaceutical chemists, utilizing standard pharmaceutical excipients such as syrup, gum arabic, gelatin, sorbit, tragacanth, polyvinylpyrrolidone, lactose, glucose, corn
- 6 -1~78736 starch, calcium phosphate, glycine, magnesium stearate, talc, polyethylene glycol, silica, potato starch, sodium lauryl sulfate and so on. Tablets can contain correctives, dye stuffs, lubrieants and so on.
Oral adminstration may also be effected using a liquid formulation, for example, water or oil emulsion, solution, s~rup, elixir, and other forms. Dried matter which is dissolved in water or other vehicles before use is also acceptable. These liquid preparations can contain the acceptable additives, for example, sorbit syrup, methyl-cellulose, glucose/sugar syrup, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel, oil, wax lecithin, monooleic sorbitan, gum arabic, almond oil, frac-tionated coconut butter, oil esters, propylene glycol, ethyl alcohol, methyl p-hydroxybenzoate, propyl p-hvdroxybenzoate, sorbic acid, and if necessary, dye stuffs, perfumes and so on.
Injectable compositions can contain aseptics and solubilizers. The compositions are also acceptable in the form of suspension, solution or emulsion, and can contain suspenders, stabilizers, dispersers and so on. On the other hand, active component may be presented in the powdery form which is dissolved in an appropriate vehicle such as pyrogen-free sterilized water before use.
These compositions can contain, at least, more than 0.1 ~ by weight, preferably 10 - 60 ~ by weight of the active compound. In the case that the composition is ; composed of the unit dosage form, it should preferably contain 5 - 250 mg of the active component.
When Compound A is administered intravenously, it should preferably be formulated to soluble forms such as the sodium salt or the hydrochloride.
Representative compositions containing the active component follow in the examples. ~;
Example l (Injectable composition) Sterile 4-carbamoyl-5-hydroxyimidazole hydro-chloride (10 mg) was aseptically put into an ampoule and sealed to prevent from humidity and microbial contamination.
Before use, it was dissolved in 2 ml of 0.5 % (w/v) lidocaine solution.
Example 2 (Injectable composition) Manufacturing procedures were identical with Example 1 except the content of the active component (250 ` mg).
ExamPle 3 (Injectable composition) Sterile sodium 4-carboamoyl-5-hydroxyimidazolate -~ (250 mg) was aseptically put into an ampoule and sealed to ` prevent from humidity and microbial contamination. Before --3 :' `
s use, it was dissolved in 2 ml of 0.5 % (w/v) lidocaine ~ 20 solution. r ~ ;., ~ ;
Example 4 (Injectable composition) ~ Manufacturing procedures were identical with ,~ Example 3 except the content of the active component (10 ~ mg).
. 3 Example 5 (Tablet) 4-Carbamoyl-5-hydroxyimidazole 250 mg Mannitol 200 mg Potato starch 47 mg Magnesium stearate 3 mg Example 6 (Suppositoria) '.' , . .
~07~73~ :
4-carbamoyl-5-hydroxyimidazole 250 mg Tannic acid 15 mg Belladonna extract 10 mg Ichthammol 100 mg Ethylaminobenzoate 50 mg Cacaobutter 750 mg Example 7 (Suppositoria) 4-Carbamoyl-5-hydroxyimidazole S00 mg Tannic acid 30 mg . Belladonna extract 20 mg Ichthammol 200 mg .. . . Ethylaminobenzoate 100 mg Cacaobutter 1500 mg In addition, the said active component can be formulated to unguent, troche and so on in a manner well-known to pharmaceutical chemists.
What is claimed is:
: ,~
~ .
~ .-,~, ; .,r~j ':''i .;~
.
., ~ .
.,`J, r ., _ 9 _ ' ', :, :' '
Oral adminstration may also be effected using a liquid formulation, for example, water or oil emulsion, solution, s~rup, elixir, and other forms. Dried matter which is dissolved in water or other vehicles before use is also acceptable. These liquid preparations can contain the acceptable additives, for example, sorbit syrup, methyl-cellulose, glucose/sugar syrup, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel, oil, wax lecithin, monooleic sorbitan, gum arabic, almond oil, frac-tionated coconut butter, oil esters, propylene glycol, ethyl alcohol, methyl p-hydroxybenzoate, propyl p-hvdroxybenzoate, sorbic acid, and if necessary, dye stuffs, perfumes and so on.
Injectable compositions can contain aseptics and solubilizers. The compositions are also acceptable in the form of suspension, solution or emulsion, and can contain suspenders, stabilizers, dispersers and so on. On the other hand, active component may be presented in the powdery form which is dissolved in an appropriate vehicle such as pyrogen-free sterilized water before use.
These compositions can contain, at least, more than 0.1 ~ by weight, preferably 10 - 60 ~ by weight of the active compound. In the case that the composition is ; composed of the unit dosage form, it should preferably contain 5 - 250 mg of the active component.
When Compound A is administered intravenously, it should preferably be formulated to soluble forms such as the sodium salt or the hydrochloride.
Representative compositions containing the active component follow in the examples. ~;
Example l (Injectable composition) Sterile 4-carbamoyl-5-hydroxyimidazole hydro-chloride (10 mg) was aseptically put into an ampoule and sealed to prevent from humidity and microbial contamination.
Before use, it was dissolved in 2 ml of 0.5 % (w/v) lidocaine solution.
Example 2 (Injectable composition) Manufacturing procedures were identical with Example 1 except the content of the active component (250 ` mg).
ExamPle 3 (Injectable composition) Sterile sodium 4-carboamoyl-5-hydroxyimidazolate -~ (250 mg) was aseptically put into an ampoule and sealed to ` prevent from humidity and microbial contamination. Before --3 :' `
s use, it was dissolved in 2 ml of 0.5 % (w/v) lidocaine ~ 20 solution. r ~ ;., ~ ;
Example 4 (Injectable composition) ~ Manufacturing procedures were identical with ,~ Example 3 except the content of the active component (10 ~ mg).
. 3 Example 5 (Tablet) 4-Carbamoyl-5-hydroxyimidazole 250 mg Mannitol 200 mg Potato starch 47 mg Magnesium stearate 3 mg Example 6 (Suppositoria) '.' , . .
~07~73~ :
4-carbamoyl-5-hydroxyimidazole 250 mg Tannic acid 15 mg Belladonna extract 10 mg Ichthammol 100 mg Ethylaminobenzoate 50 mg Cacaobutter 750 mg Example 7 (Suppositoria) 4-Carbamoyl-5-hydroxyimidazole S00 mg Tannic acid 30 mg . Belladonna extract 20 mg Ichthammol 200 mg .. . . Ethylaminobenzoate 100 mg Cacaobutter 1500 mg In addition, the said active component can be formulated to unguent, troche and so on in a manner well-known to pharmaceutical chemists.
What is claimed is:
: ,~
~ .
~ .-,~, ; .,r~j ':''i .;~
.
., ~ .
.,`J, r ., _ 9 _ ' ', :, :' '
Claims (5)
1. A therapeutic composition for use in the treat-ment of cancer, rheumatism and/or nephritis which com-prises an effective amount of 4-carbamoyl-5-hydroxy-imidazole or its pharmaceutically acceptable salt as an active ingredient and a pharmaceutically acceptable carrier or diluent.
2. The composition according to claim 1 comprising a tablet or capsule for oral administration containing 5 - 250 mg of the active ingredient.
3. The composition according to claim 1 comprising a liquid formulation for oral administration containing 5 - 250 mg of the active ingredient.
4. The composition according to claim 1 comprising an injectable composition containing 5 - 250 mg of the active ingredient.
5. The composition according to claim 2, 3 or 4 wherein the active ingredient comprises 10 - 60 % by weight of the composition.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51107520A JPS604802B2 (en) | 1976-09-07 | 1976-09-07 | anticancer drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1078736A true CA1078736A (en) | 1980-06-03 |
Family
ID=14461270
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA286,281A Expired CA1078736A (en) | 1976-09-07 | 1977-09-07 | Therapeutic application of 4-carbamoyl-5-hydroxyimidazole |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS604802B2 (en) |
| AU (1) | AU509455B2 (en) |
| CA (1) | CA1078736A (en) |
| DE (1) | DE2740281A1 (en) |
| FR (1) | FR2363329A1 (en) |
| NL (1) | NL7709853A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4582845A (en) * | 1980-11-05 | 1986-04-15 | Sumitomo Pharmaceuticals Co., Ltd. | Pharmaceutical composition for injection |
| US4728729A (en) * | 1984-03-14 | 1988-03-01 | Sumitomo Pharmaceuticals Co., Ltd. | Cyanoimidazole nucleoside derivatives |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU507066B1 (en) * | 1977-09-06 | 1980-01-31 | Sumitomo Chemical Company, Limited | 2-Substituted-5-Hydroxy-1h-Imidazole 4-Carbozamide Derivatives |
| JPS5495568A (en) * | 1978-01-06 | 1979-07-28 | Sumitomo Chem Co Ltd | Novel imidazoleacetic acid derivative |
| AU530916B2 (en) * | 1979-08-08 | 1983-08-04 | Sumitomo Chemical Company, Limited | 4-carbamoyl imidazolium-5-olate derivatives |
| JPS5780317A (en) * | 1980-11-05 | 1982-05-19 | Sumitomo Chem Co Ltd | Preparation of pharmaceutical composition for injection |
| US4464531A (en) * | 1981-04-20 | 1984-08-07 | Sumitomo Chemical Company, Limited | 4-Carbamoylimidazolium-5-olate derivatives |
| JPS6089418A (en) * | 1983-10-20 | 1985-05-20 | Sumitomo Chem Co Ltd | Sustained release carcinostatic agent |
| US6750420B1 (en) * | 1998-11-13 | 2004-06-15 | Elpatronic Ag | Method for welding tubes and device for carrying out said method |
| JP5266010B2 (en) | 2007-09-14 | 2013-08-21 | 富士フイルム株式会社 | 4-Carbamoyl-5-hydroxy-imidazole derivative sulfonate compound |
| WO2014112531A1 (en) | 2013-01-15 | 2014-07-24 | 富士フイルム株式会社 | Package for solid preparation including 5-hydroxy-1h-imidazole-4-carboxamide or salt or hydrate thereof |
| EP2946780B1 (en) | 2013-01-15 | 2017-03-01 | FUJIFILM Corporation | Tablet containing 5-hydroxy-1h-imidazole-4-carboxamide |
| JP6001684B2 (en) * | 2013-01-15 | 2016-10-05 | 富士フイルム株式会社 | 5-hydroxy-1H-imidazole-4-carboxamide sulfate |
| KR101856889B1 (en) | 2014-01-10 | 2018-05-10 | 후지필름 가부시키가이샤 | 5-hydroxy-1h-imidazole-4-carboxamide effective-dose/sensitivity prediction method and prediction device, xanthosine-monophosphate-amount measurement method, and myelodysplastic-syndrome treatment agent and treatment method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52101855A (en) * | 1976-02-21 | 1977-08-26 | Toyo Seisakusho Kk | Air moistener |
-
1976
- 1976-09-07 JP JP51107520A patent/JPS604802B2/en not_active Expired
-
1977
- 1977-09-07 FR FR7727134A patent/FR2363329A1/en active Granted
- 1977-09-07 AU AU28619/77A patent/AU509455B2/en not_active Expired
- 1977-09-07 CA CA286,281A patent/CA1078736A/en not_active Expired
- 1977-09-07 DE DE19772740281 patent/DE2740281A1/en not_active Ceased
- 1977-09-07 NL NL7709853A patent/NL7709853A/en not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4582845A (en) * | 1980-11-05 | 1986-04-15 | Sumitomo Pharmaceuticals Co., Ltd. | Pharmaceutical composition for injection |
| US4728729A (en) * | 1984-03-14 | 1988-03-01 | Sumitomo Pharmaceuticals Co., Ltd. | Cyanoimidazole nucleoside derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2861977A (en) | 1979-03-15 |
| FR2363329A1 (en) | 1978-03-31 |
| DE2740281A1 (en) | 1978-03-09 |
| NL7709853A (en) | 1978-03-09 |
| JPS604802B2 (en) | 1985-02-06 |
| AU509455B2 (en) | 1980-05-15 |
| JPS5332124A (en) | 1978-03-27 |
| FR2363329B1 (en) | 1981-01-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1078736A (en) | Therapeutic application of 4-carbamoyl-5-hydroxyimidazole | |
| Conti et al. | Protective activity of silipide on liver damage in rodents | |
| US5008242A (en) | Treatment of inflammation using 1-antichymotrypsin | |
| US4181731A (en) | Novel therapeutic application of 4-carbamoyl-5-hydroxyimidazole | |
| US6063814A (en) | Phorbol esters as anti-neoplastic and white blood cell elevating agents | |
| EP0066918A1 (en) | Anti-inflammatory compositions exhibiting minimized gastric damage | |
| JP2001513506A (en) | Chromium / biotin treatment for type II diabetes | |
| US4963559A (en) | Method of treating cancer and cancer metastasis | |
| LONGCOPE et al. | The use of BAL (British anti-Lewisite) in the treatment of the injurious effects of arsenic, mercury and other metallic poisons | |
| EP0313654B1 (en) | Drug for prophylaxis and treatment of hepatopathy | |
| KR100207356B1 (en) | Cancerous metastasis inhibitor | |
| JPS63270626A (en) | Antiulcer agent | |
| US5661188A (en) | Therapeutic uses for sodium 2-mercaptoethanesulphonate (mesna) | |
| KR100310121B1 (en) | Treatment of tumor diseases using thiazopurine and ribavirin | |
| WO1989005637A1 (en) | Improving toxicity profiles in chemotherapy | |
| JP2688057B2 (en) | Anti-adenocarcinoma | |
| US4814353A (en) | Therapeutic and prophylactic agent for gastritis | |
| US5116600A (en) | Composition and method for inhibiting inflammation caused by non-parenteral administration of 5-fluorouracil type compounds | |
| Chrysant et al. | Hemodynamic and metabolic effects of hypomagnesemia in spontaneously hypertensive rats | |
| MXPA97000967A (en) | Therapeutic use of acetazolamide for the treatment of edema cereb | |
| EP0140958B1 (en) | Oncolytic drug combinations | |
| US6306901B1 (en) | Agent for prophylaxis and therapy of diseases | |
| CA2000469A1 (en) | Method of improving post-ischemic myocardial dysfunction using and ace inhibitor alone or in combination with a thrombolytic agent and combination | |
| KR20020031404A (en) | Blood plasma replacement solution | |
| US4963588A (en) | Use of ubenimex for treating myelodysplastic syndrome |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |