Sustained-release prostaglandin I derivative preparation

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.