WO2001024784A2 - New use - Google Patents
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- WO2001024784A2 WO2001024784A2 PCT/JP2000/006874 JP0006874W WO0124784A2 WO 2001024784 A2 WO2001024784 A2 WO 2001024784A2 JP 0006874 W JP0006874 W JP 0006874W WO 0124784 A2 WO0124784 A2 WO 0124784A2
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- Prior art keywords
- inhibitor
- plasminogen activator
- effect caused
- group
- increasing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This invention relates to a new use of a plasminogen activator, which is useful in a medical field.
- plasminogen activators are well known.
- a certain macrolide compound i.e., tacrolimus, and its related compounds are known to have preventing or treating activity of cerebral infarction (USP 5,648,351).
- This invention relates to a new use of plasminogen activators, for increasing an effect caused by interleukin 2 inhibitor (hereinafter, referred to IL-2 inhibitor) .
- IL-2 inhibitor interleukin 2 inhibitor
- one object of the present invention is to provide a new use of a plasminogen activator for increasing an effect caused by IL-2 inhibitor.
- Another object of this invention is to provide a method for increasing an effect caused by IL-2 inhibitor by administering an effective amount of a plasminogen activator.
- a further object of this invention is to provide a use of a plasminogen activator for manufacturing a medicament for increasing an effect caused by IL-2 inhibitor.
- Still further object of this invention is to provide a composition comprising a plasminogen activator, for increasing an effect caused by IL-2 inhibitor.
- the "plasminogen activator” should not be limited and be considered to mean any compounds which can convert inactivate plasminogen to the protease plasmin.
- tissue-type plasminogen activator (tPA) tissue-type plasminogen activator (tPA) , urokinase (UK), pro-urokinase, streptokinase, acylated streptokinase/tPA conjugates, etc.
- IL-2 inhibitor used in the present invention should not be limited and be considered to mean any ones possessing IL-2 inhibitory activity.
- the particular example is the one possessing an inhibitory activity on the production of IL-2.
- the other is the one that inhibits the transmission of IL-2 signal.
- the preferable "effect caused by IL-2 inhibitor” is a neuroptotective activity.
- the effect caused by IL- 2 inhibitor may be the treatment and prevention of acute or chronic cerebral neurodegenerative diseases, such as cerebral ischemic diseases and/or brain damage caused by ischemia.
- IL-2 inhibitor is, for example, the tricyclic macrolide shown in EP-0184162, WO89/05303, WO93/05058, W096/31514, and so on, the disclosure of which is incorporated herein by reference. It is well known that those tricyclic macrolides have strong IL-2 inhibitory activity.
- the tricyclic compound of the following formula (I) can be exemplified.
- R 2 is two adjacent hydrogen atoms, but R 2 may also be an alkyl group or
- (b) may form another bond formed between the carbon atoms to which they are attached;
- R 7 is a hydrogen atom, a hydroxy group, a protected hydroxy group, or an alkoxy group, or an oxo group together with
- R 1 ; R 8 and R 9 are independently a hydrogen atom or a hydroxy group
- R 10 is a hydrogen atom, an alkyl group, an alkyl group substituted by one or more hydroxy groups, an alkenyl group, an alkenyl group substituted by one or more hydroxy groups, or an alkyl group substituted by an oxo group
- X is an oxo group, (a hydrogen atom and a hydroxy group) , (a hydrogen atom and a hydrogen atom) , or a group represented by the formula -CH 2 0-
- Y is an oxo group, (a hydrogen atom and a hydroxy group),
- R u and R 12 are independently a hydrogen atom, an alkyl group, an aryl group or a tosyl group
- R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 22 and R 23 are independently a hydrogen atom or an alkyl group
- R 24 is an optionally substituted ring system which may contain one or more heteroatoms
- n is an integer of 1 or 2
- Y, R 10 and R 23 together with the carbon atoms to which they are attached, may represent a saturated or unsaturated 5- or 6-membered nitrogen, sulfur and/or oxygen containing heterocyclic ring optionally substituted by one or more groups selected from the group consisting of an alkyl, a hydroxy, an alkoxy, a benzyl, a group of the formula -
- lower means, unless otherwise indicated, a group having 1 to 6 carbon atoms .
- alkyl groups and an alkyl moiety of the "alkoxy group” include a straight or branched chain aliphatic hydrocarbon residue, for example, a lower alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, neopentyl and hexyl .
- alkenyl groups include a straight or branched chain aliphatic hydrocarbon residue having one double-bond, for example, a lower alkenyl group such as vinyl, propenyl (e.g., allyl group), butenyl, methylpropenyl, pentenyl and hexenyl .
- a lower alkenyl group such as vinyl, propenyl (e.g., allyl group), butenyl, methylpropenyl, pentenyl and hexenyl .
- aryl groups include phenyl, tolyl, xylyl, cumenyl, mesityl and naphthyl .
- Preferable protective groups in the "protected hydroxy groups" and the "protected amino" are 1- (lower alkylthio) - (lower) alkyl group such as a lower alkylthiomethyl group (e.g., methylthiomethyl, ethylthiomethyl, propylthiomethyl, isopropylthiomethyl, butylthiomethyl, isobutylthiomethyl, hexylthiomethyl, etc.), more preferably C x -C 4 alkylthiomethyl group, most preferably methylthiomethyl group; trisubstituted silyl group such as a tri (lower) alkylsilyl (e.g., trimethylsilyl, triethylsilyl, tributylsilyl, tert- butyldimethylsilyl, tri-tert-butylsilyl, etc.) or lower alkyl-diarylsilyl (e.g., methyl
- alkylsilyl group more preferably tri (C 1 -C 4 ) alkylsilyl group and C ⁇ C, alkyldiphenylsilyl group, most preferably tert- butyldimethylsilyl group and tert-butyldiphenylsilyl group; and an acyl group such as an aliphatic, aromatic acyl group or an aliphatic acyl group substituted by an aromatic group, which are derived from a carboxylic acid, sulfonic acid or carbamic acid.
- aliphatic acyl groups include a lower alkanoyl group optionally having one or more suitable substituents such as carboxy, e.g., formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, carboxyacetyl, carboxypropionyl, carboxybutyryl, carboxyhexanoyl, etc.; a cyclo (lower) alkoxy (lower) alkanoyl group optionally having one or more suitable substituents such as lower alkyl, e.g., cyclopropyloxyacetyl, cyclobutyloxypropionyl , cycloheptyloxybutyryl, menthyloxyacetyl, menthyloxypropionyl, menthyloxybutyryl, menthyloxypentanoyl, menthyloxyhexanoyl
- aromatic acyl groups include an aroyl group optionally having one or more suitable substituents such as nitro, e.g., benzoyl, toluoyl, xyloyl, naphthoyl, nitrobenzoyl, dinitrobenzoyl, nitronaphthoyl, etc.; and an arenesulfonyl group optionally having one or more suitable substituents such as halogen, e.g., benzenesulfonyl, toluenesulfonyl, xylenesulfonyl, naphthalenesulfonyl, fluorobenzenesulfonyl, chlorobenzenesulfonyl, bromobenzenesulfonyl, iodobenzenesulfonyl, etc.
- suitable substituents such as nitro, e.g., benzoyl, toluoyl, xy
- Examples of the aliphatic acyl groups substituted by an aromatic group include ar (lower) alkanoyl group optionally having one or more suitable substituents such as lower alkoxy or trihalo (lower) alkyl, e.g., phenylacetyl, phenylpropionyl, phenylbutyryl, 2-trifluoromethyl-2-methoxy-2-phenylacetyl, 2-ethyl-2-trifluoromethyl-2-phenylacetyl, 2-trifluoromethyl- 2-propoxy-2-phenylacetyl, etc.
- ar (lower) alkanoyl group optionally having one or more suitable substituents such as lower alkoxy or trihalo (lower) alkyl, e.g., phenylacetyl, phenylpropionyl, phenylbutyryl, 2-trifluoromethyl-2-methoxy-2-phenylacetyl, 2-ethyl-2-trifluoromethyl
- More preferable acyl groups among the aforesaid acyl groups are C 1 -C 4 alkanoyl group optionally having carboxy, cyclo (C 5 - C 6 ) alkoxy (C j -C ⁇ alkanoyl group having two (C j -C,,) alkyls at the cycloalkyl moiety, camphorsulfonyl group, carboxy- (C- C 4 ) alkylcarbamoyl group, tri (C j -C alkylsilyl (C j -C 4 ) alkoxycarbonyl (C ⁇ -C - alkylcarbamoyl group, benzoyl group optionally having one or two nitro groups, benzenesulfonyl group having halogen, or phenyl (C j -C 4 ) alkanoyl group having C j -C 4 alkoxy and trihalo (C x - C 4 ) alkyl group
- the most preferable ones are acetyl, carboxypropionyl, menthyloxyacetyl, camphorsulfonyl, benzoyl, nitrobenzoyl, dinitrobenzoyl, iodobenzenesulfonyl and 2- trifluoromethyl-2-methoxy-2-phenylacetyl .
- Preferable examples of the "5- or 6-membered nitrogen, sulfur and/or oxygen containing heterocyclic ring" include a pyrrolyl group and a tetrahydrofuryl group.
- R 24 is an optionally substituted ring system which may contain one or more heteroatoms .
- Preferable R 24 may be cyclo (C 5 . 7 ) alkyl group optionally having suitable substituents, and the following ones can be exemplified.
- acyl moiety optionally contains either a dimethylamino group which may be quaternized, or a carboxy group which may be esterified
- acyl moiety optionally contains either a dimethylamino group which may be quaternized, or a carboxy group which may be esterified
- amino and/or hydroxy groups which may be protected, or aminooxalyloxymethyl .
- a preferred example is a 2- formyl-cyclopentyl group.
- a heteroaryl which may be substituted by suitable substituents moiety of the "heteroaryloxy which may be substituted by suitable substituents” may be the ones exemplified for R 1 of the compound of the formula of EP-A-532, 088, with preference given to 1-hydroxyethylindol -5-yl, the disclosure of which is incorporated herein by reference.
- ticyclic compounds (I) and its pharmaceutically acceptable salt for use in accordance with this invention are well known to have excellent i munosuppressive activity, antimicrobial activity and other pharmacological activities and, as such, be of value for the treatment or prevention of rejection reactions by transplantation of organs or tissues, graft-vs-host diseases, autoimmune diseases, and infectious diseases [EP-A-0184162, EP-A-0323042, EP-A-423714, EP-A-427680, EP-A-465426, EP-A-480623, EP-A-532088, EP-A-532089, EP-A-569337, EP-A-626385, WO89/05303, WO93/05058, W096/31514, W091/13889, W091/19495, WO93/04680, WO93/5059, etc. ] , the disclosures of which are incorporated herein by reference.
- the FK506 (general name: tacrolimus) of the following chemical formula, in particular, is a representative compound.
- the preferred examples of the tricyclic compounds (I) are the ones, wherein each of adjacent pairs of R 3 and R 4 or R 5 and R 6 independently form another bond formed between the carbon atoms to which they are attached; each of R 8 and R 23 is independently a hydrogen atom; R 9 is a hydroxy group; R 10 is a methyl group, an ethyl group, a propyl group or an allyl group; X is (a hydrogen atom and a hydrogen atom) or an oxo group; Y is an oxo group; each of R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 22 is a methyl group; R 24 is a 3-R 20 -4-R 21 -cyclohexyl group, in which R 20 is hydroxy, an alkoxy group, an oxo group, or a -OCH 2 OCH 2 CH 2 OCH 3 group, and R 21 is hydroxy, -OCN, an alkoxy group,
- tricyclic compounds (I) is, in addition to FK506, ascomycin derivatives such as halogenated-ascomycin (e.g., 33-epi-chloro-33-desoxyascomycin) , which is disclosed in EP 427,680, example 66a.
- ascomycin derivatives such as halogenated-ascomycin (e.g., 33-epi-chloro-33-desoxyascomycin) , which is disclosed in EP 427,680, example 66a.
- rapamycin [THE MERCK INDEX (12th edition), No. 8288] and its derivatives can be exemplified.
- Preferred example of the derivatives is an O-substituted derivative in which the hydroxy in position 40 of formula A illustrated at page 1 of WO 95/16691, incorporated herein by reference, is replaced by -OR j in which Rj is hydroxyalkyl, hydroalkoxyalkyl, acylaminoalkyl and aminoalkyl; for example 40-O- (2-hydroxy) ethyl-rapamycin, 40- O- ( 3-hydroxy) propyl-rapamycin, 40-O- [2- (2- hydroxy) ethoxy] ethyl-rapamycin and 40-O- (2-acetaminoethyl) - rapamycin.
- O-substituted derivatives may be produced by reacting rapamycin (or dihydro or deoxo-rapamycin) with an organic radical attached to a leaving group (for example RX where R is the organic radical which is desired as the O-substituent, such as an alkyl, allyl, or benzyl moiety, and X is a leaving group such as CC1 3 C(NH)0 or CF 3 S0 3 ) under suitable reaction conditions.
- a leaving group for example RX where R is the organic radical which is desired as the O-substituent, such as an alkyl, allyl, or benzyl moiety, and X is a leaving group such as CC1 3 C(NH)0 or CF 3 S0 3
- the conditions may be acidic or neutral conditions, for example in the presence of an acid like trifluoromethanesulfonic acid, camphorsulfonic acid, p-toluenesulfonic acid or their respective pyridinium or substituted pyridinium salts when X is CC1 3 C(NH)0 or in the presence of a base like pyridine, a substituted pyridine, diisopropylethylamine or pentamethylpiperidine when X is CF 3 S0 3 .
- the most preferable one is 40-O- (2-hydroxy) ethyl rapamycin, which is disclosed in WO94/09010, the disclosure of which is incorporated herein by reference.
- the tricyclic compounds (I) , and rapamycin and its derivatives may be in a form of its salt, which includes conventional non-toxic and pharmaceutically acceptable salt such as the salt with inorganic or organic bases, specifically, an alkali metal salt such as sodium salt and potassium salt, an alkali earth metal salt such as calcium salt and magnesium salt, an ammonium salt and an amine salt such as triethylamine salt and N-benzyl-N-methylamine salt.
- an alkali metal salt such as sodium salt and potassium salt
- an alkali earth metal salt such as calcium salt and magnesium salt
- an ammonium salt and an amine salt such as triethylamine salt and N-benzyl-N-methylamine salt.
- the tricyclic macrolide compounds there may be conformers and one or more stereoisomers such as optical and geometrical isomers due to asymmetric carbon atom(s) or double bond(s), and such conformers and isomers are also included within the scope of the present invention.
- the tricyclic macrolide compounds can be in the form of a solvate, which is included within the scope of the present invention.
- the solvate preferably include a hydrate and an ethanolate.
- IL-2 inhibitor is cyclosporin and its derivatives such as cyclosporin A, B, C, D, E, F, G, etc, which are shown in THE MERCK INDEX (12th edition) , No.2821, USP 4,117,118, 4,215,199, 4,288,431, 4,388,307, Helv. Chim. Acta. 60, 1568(1977) and 65, 1655(1982), Transplant. Proc. 17, 1362(1985), and so on.
- the most preferable one is cyclosporin A.
- the disclosures of the above references are incorporated herein.
- the tricyclic compounds (I) and its pharmaceutically acceptable salts, and cyclosporin or its derivatives may be classified as "IL-2 production inhibitor", which show immunosuppressive activity by inhibiting the production of IL-2.
- rapamycin or its derivatives may be classified as " IL-2 signal transmission inhibitor", which show immunosuppressive activity by inhibiting the transmission of IL-2 signal.
- plasminogen activators in the present invention is used in the form of a conventional pharmaceutical preparation in admixture with a conventional pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral or external administration.
- a conventional pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral or external administration.
- the pharmaceutical preparation may be compounded in a solid form such as granule, capsule, tablet, dragee, suppository or ointment, or in a liquid form such as solution, suspension or emulsion for injection, intravenous drip, ingestion, eye drop, etc.
- auxiliary substance such as stabilizing agent, wetting or emulsifying agent, buffer or any other commonly used additives.
- the plasminogen activators as the effective ingredient may usually be administered in an amount which can activate plasminogen to plasmine.
- it may be a unit dose of 0.001 mg/kg to 500 mg/kg, preferably 0.01 mg/kg to 10 mg/kg, 1 to 4 times a day.
- the above dosage may be increased or decreased according to age, body weight and conditions of the patient or administering method.
- this composition For applying this composition to a human, it is preferable to apply it by injection.
- a plasminogen activator is able to be administered for increasing the effect caused by a IL-2 inhibitor simultaneously, separately or in sequential use with a IL-2 inhibitor.
- the plasminogen activators can be mixed with the IL-2 inhibitor prior to its use.
- the composition comprising the said plasminogen activators of the present invention may further comprise the IL-2 inhibitor. And optionally, it comprises further additional ingredients, such as, mycophenolate mofetil (CellCept) , steroids, Azathiopurine, and so on.
- a daily dose thereof is about 0.01 ⁇ 1000 mg, preferably 0.05 ⁇ 500 mg, and more preferably, 0.1 ⁇ 100 mg for therapeutic purposes.
- the average unit dose may be generally about 0.1 mg, 0.5 mg, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg, 250 mg, or 500 mg.
- Thrombotic occlusion of the MCA was induced by photochemical reaction as described by Umemura et al., (1993). Briefly, male Sprague-Dawley rats (SLC, Inc.) weighting about 300g were anesthetized with halothane (4% for induction, 1.5% for maintenance) . The animals were placed in the lateral position, and the left MCA was exposed by a microsurgical approach. A stable thrombotic occlusion of MCA was produced by photochemical reaction between intravenously administered photoreactive dye, rose bengal
- TTC triphenyltetrazolium chloride
- FK506 (1 mg/kg; Prograf (Trade Name: Fujisawa pharmaceutical Co., Ltd.) was administered intravenously by a single bolus injection through the femoral vein 2 hours after occlusion of the MCA.
- a tissue-type plasminogen activator (t-PA) (1 mg/kg) which is a recombinant t-PA, ⁇ reteplase' , was administered intravenously by a bolus injection (20 % of total volume) followed by infusion (80 % of total volume) for 30 min through the femoral vein 2 hours after occlusion of the MCA.
- t-PA tissue-type plasminogen activator
- FK506 or t-PA When drugs were administered 2 hours after occlusion of the MCA, FK506 or t-PA showed a relatively small tendency of the inhibition of brain damage. However, the combination of FK506 and t-PA caused the significant reduction of ischemic brain damage and its inhibition is more than 23%, which is greater than that of FK506 or t-PA alone.
- the present invention provides useful neuroprotective agent for preventing or treating acute or chronic cerebral neurodegenerative diseases, such as cerebral ischemic diseases and/or brain damage caused by ischemia.
- cerebral infarction head injury, hemorrhage in brain such as subarachnoid hemorrhage or intracerebral hemorrhage, cerebral thrombosis, cerebral embolism, cardiac arrest, stroke (such as acute stroke) , transient ischemic attacks (TIA) , hypertensive encephalopathy, Alzheimer's disease, Huntington' s disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and so on.
- TIA transient ischemic attacks
- the present invention also provides the following inventions.
- a method for preventing and treating acute or chronic cerebral neurodegenerative diseases by administering an effective amount of a plasminogen activator and an effective amount of IL-2 inhibitor to a human being or an animal.
- a composition comprising a plasminogen activator and IL-2 inhibitor as a combined preparation for simultaneous, separate or sequential use for neuroprotective activity.
- An article of manufacture comprising packaging material and IL-2 inhibitor contained within said packaging material, wherein said IL-2 inhibitor is therapeutically effective for increasing or decreasing an effect caused by plasminogen activator, and wherein said packaging material comprises a label or a written material which indicates that said IL-2 inhibitor can be used for increasing or decreasing an effect caused by plasminogen activator.
- An article of manufacture comprising packaging material and a plasminogen activator contained within said packaging material, wherein said plasminogen activator is therapeutically effective for increasing an effect caused by IL-2 inhibitor, and wherein said packaging material comprises a label or a written material which indicates that said plasminogen activator can be used for increasing an effect caused by IL-2 inhibitor.
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Abstract
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Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00963073A EP1223969A2 (en) | 1999-10-04 | 2000-10-02 | Combined use of a plasminogen activator and il-2 inhibitors for neuroprotection |
JP2001527783A JP2003510351A (en) | 1999-10-04 | 2000-10-02 | New applications |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPQ3249 | 1999-10-04 | ||
AUPQ3249A AUPQ324999A0 (en) | 1999-10-04 | 1999-10-04 | New use |
AUPQ5643 | 2000-02-15 | ||
AUPQ5643A AUPQ564300A0 (en) | 2000-02-15 | 2000-02-15 | New use |
Publications (2)
Publication Number | Publication Date |
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WO2001024784A2 true WO2001024784A2 (en) | 2001-04-12 |
WO2001024784A3 WO2001024784A3 (en) | 2002-05-10 |
Family
ID=25646165
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2000/006874 WO2001024784A2 (en) | 1999-10-04 | 2000-10-02 | New use |
Country Status (3)
Country | Link |
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EP (1) | EP1223969A2 (en) |
JP (1) | JP2003510351A (en) |
WO (1) | WO2001024784A2 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1496936A1 (en) * | 2002-03-29 | 2005-01-19 | The Johns Hopkins University | Intraventricular hemorrhage thrombolysis |
WO2020228681A1 (en) * | 2019-05-10 | 2020-11-19 | 泰伦基国际有限公司 | Method and medicine for treating amyotrophic lateral sclerosis |
WO2021190561A1 (en) * | 2020-03-24 | 2021-09-30 | 泰伦基国际有限公司 | Method and drug for treating parkinson's disease |
WO2024094217A1 (en) * | 2022-11-04 | 2024-05-10 | 泰伦基国际有限公司 | Method for promoting pathological tdp-43 protein degradation, and drug |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2954043A1 (en) | 2014-07-24 | 2016-01-28 | Litevax B.V. | Carbohydrate ester adjuvants |
Citations (2)
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---|---|---|---|---|
US5648351A (en) * | 1992-12-29 | 1997-07-15 | Fujisawa Pharmaceutical Co., Ltd. | Use of macrolides for the treatment of cerebral ischemia |
US5945432A (en) * | 1995-12-22 | 1999-08-31 | The University Of Vermont And State Agricultural College | Thrombolytic agents and thienopyridine derivatives in acute stroke |
-
2000
- 2000-10-02 WO PCT/JP2000/006874 patent/WO2001024784A2/en not_active Application Discontinuation
- 2000-10-02 EP EP00963073A patent/EP1223969A2/en not_active Withdrawn
- 2000-10-02 JP JP2001527783A patent/JP2003510351A/en active Pending
Patent Citations (2)
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US5648351A (en) * | 1992-12-29 | 1997-07-15 | Fujisawa Pharmaceutical Co., Ltd. | Use of macrolides for the treatment of cerebral ischemia |
US5945432A (en) * | 1995-12-22 | 1999-08-31 | The University Of Vermont And State Agricultural College | Thrombolytic agents and thienopyridine derivatives in acute stroke |
Non-Patent Citations (7)
Title |
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BEDNAR M M ET AL: "COMBINATION TISSUE PLASMINOGEN ACTIVATOR AND TICLOPIDINE THERAPY INA RABBIT MODEL OF ACUTE THROMBOEMBOLIC STROKE" NEUROLOGICAL RESEARCH,XX,XX, vol. 18, no. 1, 1 February 1996 (1996-02-01), pages 45-48, XP000646532 * |
BOCHELEN D ET AL: "CALCINEURIN INHIBITORS FK506 AND SDZ ASM 981 ALLEVIATE THE OUTCOME OF FOCAL CEREBRAL ISCHEMIC/REPERFUSION INJURY" JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,AMERICAN SOCIETY FOR PHARMACOLOGY AND,US, vol. 288, no. 2, February 1999 (1999-02), pages 653-659, XP000980203 ISSN: 0022-3565 * |
BUNDICK ET AL: "FK506 AS AN AGONIST TO INDUCE INHIBITION OF INTERLEUKIN 2 PRODUCTION" TRANSPLANTATION,US,WILLIAMS AND WILKINS, BALTIMORE, MD, vol. 53, no. 5, 1992, pages 1150-1153, XP000913592 ISSN: 0041-1337 * |
KIM YANG-HEE ET AL: "Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator." SCIENCE (WASHINGTON D C), vol. 284, no. 5414, 23 April 1999 (1999-04-23), pages 647-650, XP002164663 ISSN: 0036-8075 * |
MAEDA MASASHI ET AL: "FK506 (tacrolimus) as a potential anti-stroke agent (3): Increased therapeutic efficacy with combined treatment of FK506 and recombinant tissue plasminogen activator (rt-PA) in a rat stroke model." JAPANESE JOURNAL OF PHARMACOLOGY, vol. 82, no. Suppl. 1, 2000, page 174P XP000990982 73rd Annual Meeting of the Japanese Pharmacological Society.;Yokohama, Japan; March 23-25, 2000 ISSN: 0021-5198 * |
TOUNG THOMAS J ET AL: "Neuroprotective FK506 does not alter in vivo nitric oxide production during ischemia and early reperfusion in rats." STROKE, vol. 30, no. 6, June 1999 (1999-06), pages 1279-1285, XP000980399 ISSN: 0039-2499 * |
YAGITA Y ET AL: "EFFECT OF IMMUNOSUPRESSANT FK506 ON ISCHEMIA-INDUCED DEGENERATION OF HIPPOCAMPAL NEURONS IN GERBILS" LIFE SCIENCES,PERGAMON PRESS, OXFORD,GB, vol. 59, no. 19, 1996, pages 1643-1650, XP000980211 ISSN: 0024-3205 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1496936A1 (en) * | 2002-03-29 | 2005-01-19 | The Johns Hopkins University | Intraventricular hemorrhage thrombolysis |
EP1496936A4 (en) * | 2002-03-29 | 2008-05-21 | Univ Johns Hopkins | Intraventricular hemorrhage thrombolysis |
WO2020228681A1 (en) * | 2019-05-10 | 2020-11-19 | 泰伦基国际有限公司 | Method and medicine for treating amyotrophic lateral sclerosis |
CN113795274A (en) * | 2019-05-10 | 2021-12-14 | 泰伦基国际有限公司 | Method and medicine for treating amyotrophic lateral sclerosis |
EP3967322A4 (en) * | 2019-05-10 | 2022-06-08 | Talengen International Limited | Method and medicine for treating amyotrophic lateral sclerosis |
WO2021190561A1 (en) * | 2020-03-24 | 2021-09-30 | 泰伦基国际有限公司 | Method and drug for treating parkinson's disease |
WO2024094217A1 (en) * | 2022-11-04 | 2024-05-10 | 泰伦基国际有限公司 | Method for promoting pathological tdp-43 protein degradation, and drug |
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EP1223969A2 (en) | 2002-07-24 |
JP2003510351A (en) | 2003-03-18 |
WO2001024784A3 (en) | 2002-05-10 |
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