Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1992-11-16
1994-11-22
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548183, 514912, A61K 31425
Patent
active
053669851
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a method of preparing a stable aqueous suspension. More particularly, the invention relates to a method of preparing a stable aqueous suspension of 5-(3-ethoxy-4-n-pentyloxyphenyl)thiazolidine-2,4-dione which is useful for the prevention and treatment of, inter alia, diabetic cataract, keratopathy and diseases of the iris and cilia.
BACKGROUND ART
The active ingredient of the aqueous suspension obtainable by the method of the invention, namely 5-(3-ethoxy-4-n-pentyloxyphenyl)thiazolidine-2,4-dione (hereinafter sometimes referred to briefly as CT-112), is a known compound having aldose reductase inhibitory activity. It has been demonstrated that this compound exerts prophylactic and therapeutic effects on chronic symptoms of diabetic cataract, neuropathy and retinopathy in mammals inclusive of man (Japanese Kokai Patent Application No. 57-28075) and therapeutic efficacy in diseases of the iris and cilia (Japanese Kokai Patent Application No. 61-43114).
When an aqueous preparation of CT-112, such as eyedrops or an injection, is to be manufactured for the treatment or prevention of the above-mentioned diseases, it is necessary to suspend the compound in water because CT-112 is only sparingly soluble in water over the pH range which is acceptable for a topical drug or an injection.
However, if such an aqueous suspension is prepared by the conventional pharmaceutical procedure, for example by dispersing the bulk powder of CT-112 directly in water or dissolving it in an appropriate solvent and, then, processing the solution into an aqueous suspension, the resulting aggregation of CT-112 or entrapment thereof in foams in the course of manufacture or adsorption of CT-112 on the container wall will lead to decreases in content and poor dispersion, thus making it extremely difficult to provide a stable aqueous CT-112 suspension.
Accordingly the inventors of the present invention explored into this field of technology for overcoming the above-mentioned drawbacks and found surprisingly that a stable aqueous suspension free from the above disadvantages can be successfully prepared by providing an aqueous solution of CT-112 whose pH has been previously adjusted to a certain value and then adjusting the pH of said aqueous solution in the presence of a defined water-soluble macromolecular compound.
DISCLOSURE OF THE INVENTION
The present invention is directed to: 5-(3-ethoxy-4-n-pentyloxyphenyl)-thiazolidine-2,4-dione characterized by adding an acid to an aqueous solution prepared by dissolving one or more members selected from the water-soluble macromolecular compound group consisting of polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropylmethylcellulose, methylcellulose and hydroxyethylcellulose and 5-(3-ethoxy-4-n-pentyloxyphenyl)thiazolidine-2,4-dione in water and having a pH value of not lower than 8 to adjust said aqueous solution to a pH value not higher than 7 and suspension of finely divided 5-(3-ethoxy-4-n-pentyloxyphenyl)thiazolidine-2,4-dione having a particle diameter of not greater than 10 .mu.m.
5-(3-Ethoxy-4-n-pentyloxyphenyl)thiazolidine-2,4-dione (CT-112), which is used as the active ingredient of the aqueous suspension of the invention, can be synthesized by the process described in Japanese Kokai Patent Application No. 57-28075 or any relevant process analogous thereto. CT-112, which can be used in the preparation of an aqueous suspension of the present invention, may be the free compound or an alkali metal salt thereof, such as the sodium salt, the potassium salt or the like.
Preparation of an aqueous suspension according to the present invention can be carried out in the following manner. First, an aqueous solution having a pH value of not lower than 8 is prepared from one or more members selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropylmethylcellulose, methylcellulose and hydroxyethylcellulose (hereinafter sometimes referred to collectively as a water-soluble macromolecular compound) and CT-112.
This
REFERENCES:
patent: 5192535 (1993-03-01), David
Inada Katsuhiro
Nakayama Hisayuki
Ushio Kazumichi
Gerstl Robert
Senju Pharmaceutical Co. Ltd.
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