Topical administration of 2-amino-2-(2-(4-octylphenyl)ethyl)prop

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...

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424400, 424 45, 424427, 424443, 514885, 514886, 514912, 514946, 514947, 514966, 514969, A61K 3324, A01N 5916

Patent

active

061213292

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to an external preparation 2-Amino-2-(2-(4-Octylphenyl)Ethyl)Propane-1,3-Diol Or Pharmaceutically Acceptable Salts Thereof For Topical Administration for topical administration, in more detail to an external preparation for topical administration which contains as the active ingredient 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol or pharmaceutically acceptable acid-addition salts thereof.


BACKGROUND ART

WO94/08943 discloses 2-aminopropane-1,3-diol compounds which are useful as immunosuppressive agents. Among those compounds, 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride (hereunder sometimes referred to as Compound (I)) is under research and development for the transplantation of organs and autoimmune diseases. In order to inhibit rejection reaction at organs or bone marrow and treat autoimmune diseases and allergic diseases, drugs are usually applied topically to the affected parts in addition to the oral administration. Then, it has been desirable to develop the pharmaceutical preparations of Compound (I) which can be administered through the skin, eye, lung, bronchus, nose or rectum.


DISCLOSURE OF THE INVENTION

From the point of view as above, the present inventors have made intensive investigations for the development of a pharmaceutical preparation of Compound (I) which can be administered through the skin, eye, lung, bronchus, nose or rectum, and have succeeded in formulating such pharmaceutical preparation and thereby completed the present invention.
Namely, the present invention relates to an external preparation for topical administration which contains as the active ingredient 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol or pharmaceutically acceptable acid-addition salts thereof (hereunder sometimes referred to as the compound of the present invention).
The compound of the present invention may be prepared in accordance with the methods described in WO94/08943.
The pharmaceutically acceptable acid-addition salts are inclusive of a salt with an inorganic acid such as hydrochloride, hydrobromide or sulfate, or a salt with an organic acid such as acetate, fumarate, maleate, benzoate, citrate, malate, methanesulfonate or benzenesulfonate, preferably hydrochloride. The present invention embraces the hydrate or solvate of the compound of the present invention.
The external preparation for topical administration which is applicable to the compound of the present invention includes an ointment, a paste, a liniment, a lotion, a plaster, a cataplasm, an eye drop, an eye ointment, a suppository, a fomentation, an inhalant, a spray, an aerosol, a paint, a nasal drop, a cream, a tape, a patch and the like.
The external preparation for topical administration of the present invention contains the compound of the present invention in a form of a mixture with an organic or inorganic carrier or excipient, and, for example, can be used in a form a solid, semi-solid or solution pharmaceutical preparation.
The compound of the present invention can be mixed with, for example, a non-toxic and pharmaceutically acceptable carrier which is usually employed for obtaining an external preparation for topical administration.
A carrier which can be used includes water, glucose, lactose, arabic gum, gelatin, mannitol, starch paste, magnesium trisilicate, talc, corn starch, keratin, colloid silica, potato starch, urea and other carriers which are suitable for preparing a solid, semi-solid or solution composition. Further, an adjuvant, a stabilizer, a thickener, a coloring matter or a flavoring agent can be added.
The compound of the present invention as an active ingredient of the external preparation for topical administration of the present invention can be contained in an amount enough to exhibit the desired activity depending on the symptom or severity of the diseases. In the case of the treatment of the symptom and diseases induced from immune disorder as mentioned below, the compound of the present invention can be administered by way of a topical

REFERENCES:
patent: 5011844 (1991-04-01), Fehr
patent: 5504068 (1996-04-01), Komiya et al.
patent: 5604229 (1997-02-01), Fujita et al.
Adachi et al., Design, Synthesis & Structure-Activity Relationships of 2-substituted-2-amino-1,3-propanediols: Discovery of a Novel Immunosuppressant, FTY 720, Bioorganic & Medicinal Chemistry Letters, vol. 5, No. 8, pp. 853-856, Apr. 20, 1995.
Fujita et al., Bioorganic & Medicinal Chemistry Letters, vol. 5, No. 8, 847-852 (1995).
JP 07-188046, A (LTT Institute Co., Ltd.) Jul. 25, 1995 (abstract only).
JP 06-256182, A (LTT Institute Co., Ltd.) Sep. 13, 1994 (abstract only).

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