Claims
- 1. A method of antagonizing inhibitory actions upon platelet aggregation, comprising administering to a patient having thrombocytopathy a prostaglandin I2 derivative selected from the group consisting of carbacyclin, isocarbacyclin and a meta-phenylene-form prostaglandin I2 derivative.
- 2. The platelet function increment method according to claim 1, wherein said meta-phenylene-form prostaglandin I2 derivative is a compound having the following formula (I) wherein R1 is,(A) COOR2 wherein R2 is (1) a hydrogen or a pharmacologically acceptable cation, (2) a straight-chain alkyl having 1 to 12 carbon atoms or a branched alkyl having 3 to 14 carbon atoms, (3) —Z—R3 wherein Z is a balance bond, or a straight-chain or branched alkylene shown by CtH2t, t represents an integer from 1 to 6, R3 is a cycloalkyl having 3 to 12 carbon atoms or a substituted cycloalkyl having 3 to 12 carbon atoms which is substituted with 1 to 3 substituents R4, wherein R4 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, (4) —(CH2CH2O)nCH3 wherein n is an integer from 1 to 5, (5) —Z—Ar1 wherein Z has the same meaning as defined above, Ar1 is phenyl, α-naphthyl, β-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, α-furyl, β-furyl, α-thienyl, β-thienyl or a substituted phenyl, wherein the substituent is at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, an alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl, phenoxy, p-acetamidebezamide, —CH═N—NH—C(═O)—NH2, —NH—C(═O)—Ph, —NH—C(═O)—CH3 or —NH—C(═O)—NH2), (6) —CtH2tCOOR4 wherein CtH2t and R4 have the same meanings as defined above, (7) —CtH2tN(R4)2 wherein CtH2t and R4 have the same meanings as defined above, (8) —CH(R5)—C(═O)—R6 wherein R5 is a hydrogen or benzoyl, R6 is phenyl, p-bromophenyl, p-chlorophenyl, p-biphenyl, p-nitrophenyl, p-benzamidephenyl or 2-naphthyl, (9) CpH2p—W—R7 wherein W is —CH═CH—, —CH═CR7— or —C≡C—, R7 is a hydrogen, or a straight-chain or branched alkyl or aralkyl each having 1 to 30 carbon atoms, p is an integer from 1 to 5, or, (10) —CH(CH2OR8)2 wherein R8 is an alkyl or acyl each having 1 to 30 carbon atoms, (B) —CH2OH (C) —C(═O)N(R9)2 wherein R9 is a hydrogen, a straight-chain alkyl having 1 to 12 carbon atoms, a branched alkyl having 3 to 12 carbon atoms, a cycloalkyl having 3 to 12 carbon atoms, a cycloalkylalkylene having 4 to 13 carbon atoms, phenyl, a substituted phenyl, wherein the substituent has the same meaning as defined in the above item (A) (5), an aralkyl having 7 to 12 carbon atoms or —SO2R10, where R10 is an alkyl having 1 to 10 carbon atoms, a cycloalkyl having 3 to 12 carbon atoms, phenyl, a substituted phenyl, wherein the substituent has the same meaning as defined in the above item (A)(5) or an aralkyl having 7 to 12 carbon atoms, and two of said substituents R9 may be the same or different provided that when one is —SO2R10, the other is not SO2R10, or, (D) —CH2OTHP, where THP is a tetrahydropyranyl group; A is,(1) —(CH2)m—(2) —CH═CH—CH2—(3) —CH2—CH═CH—(4) —CH2—O—CH2—(5) —CH═CH—(6) —O—CH2— or (7) —C≡C—wherein m is an integer of 1 or 2, Y is a hydrogen, an alkyl having 1 to 4 carbon atoms, chlorine, bromine, fluorine, formyl, methoxy or nitro; B is—X—C(R11)(R12)OR13 wherein R11 is a hydrogen or an alkyl having 1 to 4 carbon atoms, R13 is a hydrogen, an acyl having 1 to 14 carbon atoms, an aroyl having 6 to 15 carbon atoms, tetrahydropyranyl, tetrahydrofuranyl, 1-ethoxyethyl or t-butyl; X is,(1) —CH2—CH2—(2) —CH═CH—(3) —C≡C—, R12 is(1) a straight-chain alkyl having 1 to 12 carbon atoms, a branched alkyl having 3 to 14 carbon atoms or, (2) —Z—Ar2 wherein Z has the same meaning as defined above, Ar2 is phenyl, α-naphthyl, β-naphthyl, or a phenyl substituted with at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, an alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl or phenoxy, or (3) —CtH2tOR14 wherein CtH2t has the same meaning as defined above, R14 is a straight-chain alkyl having 1 to 6 carbon atoms, a branched alkyl having 3 to 6 carbon atoms, phenyl, a phenyl substituted with at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, an alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl or phenoxy, cyclopentyl, cyclohexyl, or a cyclopentyl or cyclohexyl each substituted with one to four straight-chain alkyl groups having 1 to 4 carbon atoms, or (4) —Z—R3 wherein Z and R3 have the same meanings as defined above, or (5) —CtH2t—CH═C(R15)R16 wherein —CtH2t has the same meaning as defined above, R15 and R 16 respectively represent a hydrogen, methyl, ethyl, propyl, or butyl, or (6) —CuH2u—C≡C—R17 wherein u is an integer from 1 to 7, CuH2u represents a straight-chain or branched alkylene, R17 is a straight-chain alkyl having 1 to 6 carbon atoms, E is a hydrogen, or —OR18 wherein R18 is an acyl having 1 to 12 carbon atoms, an aroyl having 7 to 15 carbon atoms or R2, wherein R2 has the same meaning as defined above, and this general formula represents a d-form, an l-form or a dl-form.
- 3. The platelet function increment method according to claim 1, wherein said increment agent enhances platelet aggregation induced by other stimulus without, by itself, inducing platelet aggregation.
- 4. The platelet function increment method according to claim 1, wherein said increment agent physiologically antagonizes an antiplatelet drug.
- 5. The platelet function increment method according to claim 1, wherein said increment agent inhibits increase of cyclic AMP concentrations in platelets.
- 6. The platelet function increment method according to claim 1, which is used for the purpose of treating an abnormality in release among congenital thrombocytopathy, or an acquired thrombocytopathy.
- 7. The platelet function increment method according to claim 6, wherein said abnormality in release is storage pool disease, cyclooxygenase deficiency, thromboxane A2 synthase deficiency, thromboxane A2 receptor abnormality or calcium ionophore refractory.
- 8. The platelet function increment method according to claim 6, wherein said acquired thrombocytopathy is induced by chronic renal failure, a liver disease, a blood disorder, extracorporeal circulation or a drug.
Priority Claims (1)
Number |
Date |
Country |
Kind |
8-245078 |
Sep 1996 |
JP |
|
Parent Case Info
This application is a 371 of PCT/JP97/03287 filed Sep. 17, 1997.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/JP97/03287 |
|
WO |
00 |
5/27/1998 |
5/27/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/11899 |
3/26/1998 |
WO |
A |
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Number |
Name |
Date |
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4474802 |
Ohno et al. |
Oct 1984 |
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4564620 |
Ohno et al. |
Jan 1986 |
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5416231 |
Asai et al. |
May 1995 |
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