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SUMMARY
In a first aspect of the present
invention, there is provided a
pharmaceutical composition in dosage
unit form, which comprises a dosage
effective for the treatment of
osteoporosis of a compound of
24,25-dihydroxycholecalciferol
(hereinafter referred to the present
substance) and a pharmaceutically
acceptable carrier.
In a second aspect of the present
invention, there is provided a method
for treating osteoporosis, which
comprises administering to a patient
suffering from osteoporosis an effective
amount of a compound of
24,25-dihydroxycholecalciferol.
BACKGROUND
The present invention relates to a
pharmaceutical composition for treating
osteoporosis, which contains a compound
of 24,25-dihydroxycholecalciferol as an
active ingredient.
In recent years, the average life span
of the Japanese has rapidly extended,
and accordingly the population of people
of age of more than 65 is now more than
ten millions. Consequently, the
population of the patients treated as
those suffering from osteoporosis is
presumed to be as many as 3 millions.
Accordingly, the elucidation of the
morbid state and the establishment of
the therapy of osteoporosis are very
important problems, and the development
of the safe medicine for treating
osteoporosis has been keenly expected.
Although it is considered that the
occurrence of osteoporosis is due to
several causes such as endocrinical
causes, nutritive causes, physical
causes, hereditary causes, etc., cases
of postmenopausal osteoporosis occupies
the largest percentage of all the cases
of osteoporosis.
An activated vitamin D 3 , for instance,
1α-hydoroxycholecalciferol or
1α,25-dihydroxycholecalciferol, is used
as an active ingredient of the
pharmaceutical composition for treating
osteoporosis and the activated vitamin D
3 is chemically similar to the present
substance, however, there is a
side-effect problem in the
administration of such an activated
vitamin D 3 and accordingly, it is
necessary to pay a close attention in
administering such an activated vitamin
D 3 .
In addition, although the effect of the
activated vitamin D 3 on the bones of
the patient administered therewith is
determined by the extent of promotion of
absorption of calcium via the intestinal
tracts of the patient, such a
determination is an indirect
determination and it has not been
elucidated that there is any direct
interrelationship between the extent of
promotion of absorption of calcium and
the lesion of the bone due to
osteoporosis.
In consideration of the above-mentioned
situation, the present inventors have
studied for the substance utilizable for
treating osteoporosis, particularly
among the safe and endogenous substances
present in healthy human body while
examining the antiosteoporotic activity,
thereof and as a result, the present
inventors have found out that the
compounds of
24,25-dihydroxycholecalciferol
(hereinafter abbreviated and referred to
as 24,25-(OH) 2 -D 3 , or more simply as
the present substance) have an activity
of directly improving the lesion of
bones due to osteoporosis to a
remarkable extent without exhibiting any
side-effects and toxicity, and have
attained the present invention.
Osteoporosis referred to in the present
invention includes not only senile
osteoporosis and postmenopausal
osteoporosis but also secondary
osteomalacial osteoporosis accompanying
osteomalacia, secondary osteoporosis
accompanying functional accentuation of
the accessory thyroid and topical
osteoporosis and abnormal bone both due
to articular rheumatism.
Before 20 days and 10 days before
butchering, oxytetracycline was
intraperitoneally administered to some
rats of each group at a dose rate of 15
mg/kg/time (in total, 2 times), and
after butchering the rats, the right
tibia was taken from each rat and after
fixing the tibia with aqueous 70% by
weight ethanolic solution, a specimen
was made by imbedding the fixed tibia in
a polyester resin (Ligorac) and cutting
transversally at the position 10 mm from
one end thereof. The distance between
the two marks made by oxytetracycline on
the specimen, which was determined under
a fluorescent microscope was divided by
the time period between the two
administrations of tetracycline, thereby
finding the velocity of osteogenesis
(formation of bone) per unit time, the
results being shown in Table 1.
After finishing the administration, all
rats were butchered and after collecting
the right tibia from each of the
butchered animals and preparing the
specimen of the tibia following the
above-mentioned technique, each of the
thus prepared specimens were vertically
sliced at the position of 60 to 70
micrometers from one end thereof
following the conventional method, and
the sliced specimen was subjected to
contact microradiography, to carry out
the morphological evaluation of the
tibia, the results being shown in FIGS.
1 to 3. From FIGS. 1 to 3, it is clearly
understood that the osteotrabecule which
has once disappeared by OVX was restored
in the rat of the group to which the
present substance was administered at a
dose rate of 1 microgram/kg. |
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