Claims
- 1. An orally administrable sustained release tablet of prostaglandin I derivative comprising a prostaglandin I derivative, 0.1% by weight to 30% by weight of a buffer and a hydrogel base,said derivative is a prostaglandin I derivative compound represented by the following formula (i) or a salt or ester thereof: wherein R1 is (a) COOR2 wherein R2 is 1) hydrogen of a pharmaceutically acceptable cation, 2) C1-C12 straight alkyl or C3-C14 branched alkyl, 3) —Z—R3 wherein Z is a valence bond or straight or branched alkylene represented by CtH2t wherein t is an integer of 1-6, R3 is C3-C12 cycloalkyl or C3-C12 cycloalkyl substituted with 1 to 3 R4 wherein R4 is hydrogen of C1-C5 alkyl, 4) —(CH2CH2O)nCH3 5) —Z—Ar1 wherein Z represents the same meaning as described above, Ar1 is phenyl, α-naphthyl, β-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, α-furyl, β-furyl, α-thienyl, β-thienyl or substituted phenyl, wherein the substituent is at least one selected from the group consisting of chlorine, bromine, fluorine, iodine, trifluoromethyl, C1-C4-alkyl, nitro, cyano, methoxy, phenyl, phenoxy, p-acetamidobenzamide, —CH═N—NH—C(═O)—NH2, —NH—C(═O)—Ph, —NH—C(═O)—CH3 and —NH—C(═O)—NH2—, 6) —CtH2tCOOR4 wherein CtH2t and R4 represent the same meanings as described above, 7) —CtH2tN(R4)2 wherein CtH2t and R4 represent the same meanings as described above, 8) —CH(R5)—C(═O)—R6 wherein R5 is 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 hydrogen, C1-C30 straight or branched alkyl or aralkyl, p is an integer of 1-5, or 10) —CH(CH2OR8)2 wherein R8 is C1-C30 alkyl or acyl, (b) —CH2OH (c) —C(═O)N(R9)2 wherein R9 is hydrogen, C1-C12 straight alkyl, C3-C12 branched alkyl, C3-C12 cycloalkyl, C4-C13 cycloalkylalylene, phenyl, substituted phenyl, wherein the definition of the substituents are the same as (a)5) described above, C7-C12 aralkyl or —SO2R10, wherein R10 is C1-C10 alkyl, C3-C12 cycloalkyl, phenyl, substituted phenyl, wherein the definition of the substituents are the same as (a)5) described above or C7-C12 aralkyl, with the proviso that although the two R9 may be the same or different, when one is —SO2R10, the other is not —SO2R10, or (d) —CH2OTHP wherein THP represents tetrahydropyranyl, 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 to 3, Y is hydrogen, C1-C4 alkyl, chlorine, bromine, fluorine, formyl, methoxy or nitro, B is —X—C(R11)(R12)OR13 wherein R11 is hydrogen or C1-C4 alkyl, R13 is hydrogen, C1-C14 acyl, C6-C15 aroyl, tetrahydropyranyl, tetrahydrofuranyl, l-ethoxyethyl or t-butyl, X is 1) —CH2—CH2—2) —CH═CH—3) —C≡C—R12 is 1) C1-C12 straight alkyl, C3-C14 branched alkyl, 2) —Z—Ar2 wherein Z represents the same meaning as described above, Ar2 represents phenyl, α-naphthyl, β-naphthyl or phenyl substituted with at least one substituent selected from the group consisting of chlorine, bromine, fluorine, iodine, trifluoromethyl, C1-C4-alkyl, nitro, cyano, methoxy, phenyl, phenoxy, 3) —CtH2tCOOR14 wherein CtH2t represents the same meaning as described above, R14 is C1-C6 straight alkyl, C3-C6 branched alkyl, phenyl or substituted phenyl substituted with at least one substituent selected from the group consisting of chlorine, bromine, fluorine, iodine, trifluoromethyl, C1-C4-alkyl, nitro, cyano, methoxy, phenyl, phenoxy, cyclopentyl, cyclohexyl, or cyclopenyl or cyclohexyl substituted with 1 to 4 C1-C4 straight alkyl, 4) —Z—R3 wherein Z and R3 represent the same meanings as described above, 5) —CtH2t—CH═C(R15)R16 wherein CtH2t represents the same meaning as described above, R15 and R16 independently represent hydrogen, methyl, ethyl, propyl or butyl, or 6) —CuH2u—C≡C—R17 wherein u is an integer of 1-7, CuH2u is a straight or branched alkylene, R17 is C1-C6 straight alkyl E is hydrogen or —OR18 wherein R18 is C1-C12 acyl, C7-C15 aroyl or R2 wherein R2 represents the same meaning as described above, the formula represents d-isomer, l-isomer and racemic mixture,wherein the content of the hydrogel base is 40 to 95% by weight based on the weight of the tablet to the balance of said prostaglandin I derivative, said prostaglandin I derivative being sustainedly released in a patient's gastrointestinal tract.
- 2. The sustained release tablet of prostaglandin I derivatives according to claim 1, wherein said hydrogel base consists essentially of one selected from the group consisting of methyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyethylene oxide, carboxymethyl cellulose, carboxyvinyl polymer, sodium alginate alginate and sodium hyaluronate, or a mixture of two or more of the above.
- 3. The sustained release tablet of prostaglandin I derivatives according to claim 1, wherein said buffer agent consists essentially of one selected from the group consisting of citric acid, succinic acid, fumaric acid, tartaric acid, ascorbic acid, glutamic acid, glutamine, glycine, aspartic acid, alanine, arginine, magnesium oxide, zinc oxide, magnesium hydroxide, phosphoric acid and boric acid and salts thereof, or a mixture of two or more of the above.
- 4. The sustained release tablet of prostaglandin I derivatives according to claim 1, which contains 0.1 to 10,000 μg of said prostaglandin derivative based on the weight of the preparation.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 9/61501 |
Mar 1997 |
JP |
|
Parent Case Info
This application is the national phase under 35 U.S.C. §371 of prior PCT International Application No. PCT/JP98/01057 which has an International filing date of Mar. 13, 1998 which designated the United States of America, the entire contents of which are hereby incorporated by reference.
PCT Information
| Filing Document |
Filing Date |
Country |
Kind |
| PCT/JP98/01057 |
|
WO |
00 |
| Publishing Document |
Publishing Date |
Country |
Kind |
| WO98/41210 |
9/24/1998 |
WO |
A |
US Referenced Citations (1)
| Number |
Name |
Date |
Kind |
|
5232704 |
Franz et al. |
Aug 1993 |
A |
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Non-Patent Literature Citations (1)
| Entry |
| Sadao Iguchi et al., “New Drug Development System Synthetic Technology, Base and Additives (in Japanese)”, Tokyo: R&D Planning, Jul. 12, 1985, p. 429-436. |
Patent Grant
6656502
