Agents and crystals for improving excretory potency of urinary bladder

Abstract

Agents for improving potentcy of the urinary bladder which comprise an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action. Particularly, crystals of a tricyclic, condensed, heterocyclic derivative are provided, which possess an excellent action to inhibit acetylcholinesterase and an action to improve the excretory potency of the urinary bladder. As an example, crystals of of 8-[3-[1-[(3-fluorophenyl)-methyl]-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one or a salt thereof and pharmaceutical compositions containing them are disclosed.

Description

[0001] This is a continuation-in-part of U.S. Serial No. 09 / 787,288, filed March 15, 2001.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention relates to drugs, particularly agents for further improving excretory potency of the urinary bladder. The present invention further relates to crystals and pharmaceutical compositions comprising the crystals of a tricyclic, condensed, heterocyclic compound which inhibit acetylcholinesterase and improve excretory potency of the urinary bladder. [0004] 2. Description of Related Art [0005] Inferior uropathy is a general term for subjective or objective disorders in a process through accumulation of urine (urinary storage) till excretion (urination), which may be classified into urinary cumulative disorders (incontinence of urine, pollakiuria, etc.), dysuria (difficulty of urination, scalding, obstruction of urinary tract, etc.), and the like. Inferior uropathy in the aged, particularly dysuria, especially dys...

AI Technical Summary

Benefits of technology

[0053] (12) Agent for improving excretory potency of the urinary bladder which comprises a combination of an α-blocker and an amine compound of non-carbamate-type having an acetylcholin-esterase-inhibiting action, and

[0055] As a result of intensive investigations, the present inventors have succeeded in obtaining crystals of 8-[3-[1-[(3-fluorophenyl)methyl)-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one, which are high in purity, high in quality, low in hygroscopic property, and extremely excellent in stability without deteriorating upon long-term storage under usual conditions, thereby providing the second aspect of the present invention.

Problems solved by technology

Inferior uropathy in the aged, particularly dysuria, especially dysuria caused by prostatomegaly, becomes a great problem of public concern with the advance of a recent aging society, though inferior uropathy may also be found in the youth.

Bethanechol however is incompatible with pregnant women, peptic ulcers, organic ileus, asthma, hyperthyroidism, etc., because it has adverse effects such as epiphora, sweating, gastro-intestinal disorders, stomachache, etc.

No entirely satisfactory drugs have yet been found.

However, it is known that, for example, distiginine is insufficient in its clinical efficacy since it contracts the muscle of the urinary bladder with constriction of the muscle of the urethra to increase urethral resistance and consequently make the voiding flow rate worse.

In addition, neostigmine has not been used in therapy because of the short duration of its action (Takamichi Hattori and Kosaku Yasuda, “Sinkeiinseiboukou-No-Sindan-To-Chiryou (Diagnosis and Therapy of Neurogenic Bladder)”, 2nd Ed., p.

In these compounds, however, there is neither report, suggestion nor disclosure on their effect as prophylactics or therapeutic agents for dysuria (difficulty of urination) or on their effect as excretion improving agents for urinary bladder.

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