AQUEOUS COMPOSITION
In an aqueous composition comprising a 15-keto-prostaglandin compound as an active ingredient, a polyoxyethylene castor oil derivative is admixed. By admixing a polyoxyethylene castor oil derivative, the solubility of the 15-keto-PG compound in water is increased. In a preferable embodiment, the aqueous composition may further comprise a quaternary ammonium type cationic surface active agent as a preservative. The composition of this embodiment exhibits high antimicrobial preservative effectiveness against indigenous bacterium in the eyes such as Staphylococcus aureus and therefore, the composition is especially useful as ophthalmic composition for ocular topical administration.
1 . An aqueous composition comprising a 15-keto-prostaglandin compound, characterized in that the composition comprises a polyoxyethylene castor oil derivative.
2 . The aqueous composition of claim 1 , wherein the 15-keto-prostaglandin compound is a compound of the formula (I):
wherein L, M and N are hydrogen, hydroxy, halogen, lower alkyl, hydroxy(lower)alkyl or oxo, and the five-membered ring may have at least one double bond;
A is —CH 3 , —CH 2 OH, —COCH 2 OH, —COOH or a functional derivative thereof;
B is —CH 2 —CH 2 —, —CH═CH— or —C≡C—;
R 1 is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, lower alkyl, hydroxy, oxo, aryl or heterocyclic group, and at least one carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur; and
Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon group, which is unsubstituted or substituted with halogen, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, aryloxy, heterocyclic group or heterocyclic-oxy group; lower alkoxy; lower alkanoyloxy; cyclo(lower)alkyl; cyclo(lower)alkyloxy; aryl; aryloxy; heterocyclic group; heterocyclic-oxy group.
3 . The aqueous composition of claim 1 , wherein the 15-keto-prostaglandin compound is a 15-keto-20-alkyl-prostaglandin compound.
4 . The aqueous composition of claim 3 , wherein the 15-keto-20-alkyl-prostaglandin compound is a 15-keto-20-ethyl-prostaglandin compound.
5 . The aqueous composition of claim 1 , wherein the 15-keto-prostaglandin compound is a 15-keto-16,16-dihalogen-prostaglandin compound.
6 . The aqueous composition of claim 5 , wherein the 15-keto-16,16-dihalogen-prostaglandin compound is a 15-keto-16,16-difluoro-prostaglandin compound.
7 . The aqueous composition of claim 1 , wherein the 15-keto-prostaglandin compound is a 15-keto-prostaglandin E compound or a 15-keto-prostaglandin F compound.
8 . The aqueous composition of claim 7 , wherein the 15-keto-prostaglandin F compound is a 15-keto-20-ethyl-prostaglandin F 2α compound.
9 . The aqueous composition of claim 7 , wherein the 15-keto-prostaglandin E compound is a 15-keto-prostaglandin E 1 compound.
10 . The aqueous composition of claim 7 , wherein the 15-keto-prostaglandin E compound is an 11-dehydroxy-15-keto-prostaglandin E compound.
11 . The aqueous composition of claim 1 , wherein the 15-keto-prostaglandin compound is a 13,14-dihydro-15-keto-prostaglandin compound.
12 . The aqueous composition of claim 1 , wherein the 13,14-dihydro-15-keto-prostaglandin compound is 13,14-dihydro-15-keto-20-ethyl-prostaglandin F 2 , isopropyl ester.
13 . The aqueous composition of claim 1 , wherein the polyoxyethylene castor oil derivative is polyoxyethylene 40 hydrogenated castor oil or polyoxyethylene 60 hydrogenated castor oil.
14 . The aqueous composition of claim 1 , further comprises a quaternary ammonium type cationic surface active agent.
15 . The aqueous composition of claim 14 , wherein the quaternary ammonium type cationic surface active agent is benzalkonium chloride or benzethonium chloride.
16 . The aqueous composition of claim 1 or 14 which is for topical administration.
17 . The aqueous composition of claim 16 , which is for ocular topical administration.
18 . The aqueous composition of claim 14 which is for topical administration.
19 . The aqueous composition of claim 18 , which is for ocular topical administration.