Methods for treatment of nocturia
United States Patent: 8,071,763
Issued: December 6, 2011
Inventors: Araki; Tohru
Assignee: Daiichi Sankyo
Company, Limited (Tokyo, JP)
Appl. No.: 12/387,510
Filed: May 4, 2009
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A method for the treatment of nocturia
which consists of administering to a mammal in need of such treatment a
therapeutically effective amount of a nonsteroidal anti-inflammatory drug
consisting of loxoprofen or a pharmacologically acceptable salt thereof,
wherein the mammal is a human who has a neurogenic bladder.
Description of the
FIELD OF THE INVENTION
The present invention relates to a preventive and/or therapeutic treatment
Lower urinary tract symptoms (LUTS) are becoming a major health problem
for elderly people worldwide. Nocturia a cause of insufficient sleep and
thus impaired quality of life, is one of the main problems in LUTS along
with urinary incontinence and difficulty in urination. The aetiology of
nocturia is various and complex and obscure in many patients, although
LUTS, insomnia, nocturnal polyuria due to cardiovascular or renal
hypofunction and disorders of the central nervous system (CNS) may be
among the causes (Resnick N. M., et al., Campbell's Urology, 7th edn, Vol.
2. Chapt 31. Philadelphia: Saunders, 1998: 1044-58).
The aetiology of nocturia is still obscure in many patients, even in those
with BPH. In patients whose causes of nocturia are affirmable, such as
those with LUTS, sleep disorder and nocturnal polyuria, nocturia may be
improved by effective treatment of these primary causes. Anticholinergic
drugs, hypnotics, antidiuretic hormone, Chinese herbal medicines and/or
oestrogen for female patients are usually administered for nocturia in
addition to treatments for their main diseases. However, in the inventor's
experience, about one-half of such patients do not respond well to these
As for effectiveness of nonsteroidal anti-inflammatory agents for
treatment of frequency of micturition, Al-Waili reported that in an open
trial indomethacin 100 mg suppository improved nocturia in all 15 patients
(Al-Waili, IRCS Med. Sci., 1986, 14, 322-323, 1986). In addition, Suzuki
reported a patient whose nocturia was improved with indomethacin
suppository administered as antipyretics, and added a brief comment that
some orally administered NSAIDs are also effective in nocturia (Suzuki S.,
Acta Urol. Jpn., 43, 402, 1997)
SUMMARY OF THE INVENTION
An object of the present invention is to provide a medicament which is
effective for treatment of nocturia.
The inventor has surprisingly experienced that a patient who was being
treated for BPH reported that his nocturia suddenly decreased from a usual
of four voids to one void/night when he took a 60-mg tablet of loxoprofen
sodium (loxoprofen) prescribed for his shoulder pain before sleeping.
Based on the experience, the inventor conducted a non-randomized trial
treatment with loxoprofen, a short-acting nonsteroidal anti-inflammatory
drug (NSAID) prodrug usually prescribed at a dosage of 60 mg t.i.d. for
the management of pain, in patients bothered by nocturia. As a result, the
inventor found that loxoprofen was surprisingly effective for treatment of
nocturia. The inventor also found that a class of nonsteroidal
anti-inflammatory drugs are also effective for treatment of nocturia. The
invention was achieved on the basis of these findings.
The present invention thus provides a medicament for preventive and/or
therapeutic treatment of nocturia, which comprises a nonsteroidal
anti-inflammatory drug as an active ingredient.
The present invention also provides a method for preventive and/or
therapeutic treatment of nocturia, which comprises the step of
administering to a mammal including a human in need of such treatment a
preventively and/or therapeutically effective amount of a nonsteroidal
anti-inflammatory drug, and a use of a nonsteroidal anti-inflammatory drug
for manufacture of the aforementioned medicament which comprises said
nonsteroidal anti-inflammatory drug as an active ingredient.
Among a class of nonsteroidal anti-inflammatory drugs, a class of
phenylpropionic acid-type anti-inflammatory drugs are preferred, and
loxoprofen is particularly preferred.
DETAILED DESCRIPTION OF THE INVENTION
Kinds of the nonsteroidal anti-inflammatory drugs as an active ingredient
of the medicament of the present invention are not particularly limited.
Any nonsteroidal anti-inflammatory drug can be used alone or in
combination as the active ingredient of the medicament of the present
invention. The term "nonsteroidal anti-inflammatory drug" used herein
means an anti-inflammatory drug which does not have a steroidal backbone
structure, and the scope of the nonsteroidal anti-inflammatory drugs is
readily apparent to one of ordinary skill in the art. Accordingly, the
term should not be construed any limiting sense and should be understood
in the broadest sense. In addition, the term "nonsteroidal
anti-inflammatory drug" used herein encompasses a drug in a free form, as
well as a pharmacologically acceptable salt thereof, a hydrate thereof, or
a solvate thereof. Any stereoisomer such as an optical isomer or a
diastereoisomer, or any mixture of the stereoisomer or a racemate of the
nonsteroidal anti-inflammatory drug may be used. Any novel nonsteroidal
anti-inflammatory drugs as well as any clinically available nonsteroidal
anti-inflammatory drugs may be used as active ingredients of the
medicament of the present invention. Preferred class of nonsteroidal
anti-inflammatory drugs include phenylpropionic acid-type
Examples of the nonsteroidal anti-inflammatory drugs include aspirin,
lumiracoxib, etoricoxib, parecoxib, valdecoxib, tiracoxib, rofecoxib,
celecoxib, darbufelone, dexketoprofen, aceclofenac, licofelone, bromfenac,
pranoprofen, piroxicam, nimesulide, cizolirine, ketorolac,
ibuprofen, meloxicam, lornoxicam, d-indobufen, mofezolac, nabumetone,
amtolmetin, droxicam, pranoprofen, ketoprofen, tolfenamic acid, fenoprofen,
flurbiprofen, suprofen, oxaprozin, loxoprofen, tenoxicam, zaltoprofen,
ibuprofen, alminoprofen, and tiaprofenic acid, and pharmacological salts
thereof, hydrates thereof, and solvates thereof. However, the nonsteroidal
anti-inflammatory drugs are not limited to these examples. Among them,
loxoprofen and a pharmacological salt thereof is preferred, and loxoprofen
sodium is more preferred.
The medicament of the present invention may be administered orally or
parenterally to a patient with nocturia. When a clinically available
nonsteroidal anti-inflammatory drug is used as an active ingredient of the
present invention, the available drug, per se, may be administered to a
patient with nocturia as the medicament of the present invention.
Alternatively, a pharmaceutical composition may be administered to a
patient which comprises at least one nonsteroidal anti-inflammatory drug
as the active ingredient together with at least one pharmaceutically
acceptable additive. The pharmaceutical composition can be prepared by a
method well known to those skilled in the art. Examples of the
pharmaceutical compositions suitable for oral administrations include, for
example, tablets, capsules, powders, subtilized granules, granules,
liquids, syrups and the like. Examples of the pharmaceutical compositions
suitable for parenteral administrations include, for example, injections,
suppositories, inhalants, eye drops, nasal drops, ointments, creams,
patches and the like.
The aforementioned pharmaceutical compositions may be prepared by the
addition of pharmaceutically acceptable additives to the active
ingredient. Examples of pharmaceutically acceptable additives include, for
example, excipients, disintegrators and disintegrating aids, binders,
lubricants, coating agents, colorants, diluents, base materials,
dissolving agents and dissolving aids, isotonic agents, pH modifiers,
stabilizers, propellants, adhesives and the like.
A dose of the medicaments of the present invention is not particularly
limited, and the dose can suitably be selected depending on conditions
such as, for example, route of administration, the age and body weight of
a patient, symptoms, a purpose of preventive or therapeutic treatment and
the like. For example, for oral administrations, the medicament of the
present invention may be administered in a dose of from 0.1 to 1,000 mg
per day, preferably 1 mg to 100 mg for an adult. The medicament of the
present invention may be administered once or several times a day, and
preferably, the medicament may be administered once before sleeping. For
example, when loxoprofen is administered as the medicament of the present
invention, a dose of 60 mg per day is preferred, and the dose may
preferably be administered once before sleeping. However, the dose and
mode of administration is not limited to the above example.
Claim 1 of 4 Claims
1. A method for the treatment of nocturia
which consists of administering to a human having a neurogenic bladder a
therapeutically effective amount of a nonsteroidal anti-inflammatory drug
consisting of loxoprofen or a pharmacologically acceptable salt thereof.
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