JPS61109721A - Agent for alleviating pain in osteoporosis - Google Patents

Abstract

PURPOSE:A drug for alleviating a pain in osteoporosis, containing 24,25- dihydroxycholecalciferol as an active ingredient. CONSTITUTION:The titled agent containing 24,25-dihydroxycholecalciferol [24,25-(OH)2-D3 for short] as an active ingredient. Half patients diagnosed as osteroporosis by X-rays have an appeal of lumbago or backache, etc., lumbago or backache appears when person starts to move from a rest position, and it becomes chronic. 24,25-(OH)2-D3 has an alleviating action on a pain in ostorosis. The active ingredient may be 24R,25-(OH)2-D3, 24S,25-(OH)2-D3 or their mixture, and 24R,25-D3 is especially preferable. A dose is 0.1-10,000mug, preferably 0.5-10,000mug based on adult daily, the agent may be administered orally or parenterally, and oral administration is preferable.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a pain relief agent for osteoporosis containing 24,25-dihydroxycholecalciferol.

With the average lifespan of Japanese people rapidly increasing, it is thought that as many as 3 million people may be treated as having osteoporosis, and half of the patients diagnosed with osteoporosis on X-rays have symptoms such as lower back pain. It is said that he has complaints of Low back pain first appears when moving from a resting position to exercise, and then becomes persistent.

Pain increases especially when people remain in the same position for a long time, such as sitting or standing, which is a clinically important problem, and there is a long-awaited need for an effective therapeutic agent that is safe and can be administered orally and over a long period of time. There is.

As a result of intensive research into a substance that is endogenous to healthy humans and has been proven to be safe, the present inventors discovered 24.25-dihydroxycholecalciferol (hereinafter referred to as this substance or 24.25-dihydroxycholecalciferol). The present invention was achieved based on the knowledge that the drug (abbreviated as -(0H)2-03) has a pain-reducing effect in osteoporosis, that is, it is associated with complications.

The substance may be 24R,25-(OH)-03,248°25-(OH)2-o3 or a mixture thereof, but 24R,25-(OH)2-D3 is particularly preferred. The pain relief agent for osteoporosis of the present invention can be used in various formulations as shown below, containing the above-mentioned substance as an active ingredient.

The pain-reducing agent for osteoporosis of the present invention can be administered orally or parenterally, with oral administration being preferred.

Preparations containing this substance as an active ingredient are used in dosage forms such as tablets, powders, granules, suppositories, capsules, alcoholic solutions, oily solutions, and aqueous suspensions. As the oily solvent, triglyceride esters of intermediate fatty acids, corn oil, cottonseed oil, peanut oil, fish liver oil, oily esters, etc. are used. Cocoa oil, glycerin, etc. are also preferred. Other ingredients such as lactose, starch, talc, magnesium stearate, sorbic acid, salts of sorbic acid, sugar or derivatives thereof, alcohol, physiological saline, surfactants, antioxidants, etc. may be used in combination with this substance. .

4.00002 to 4 d in unit dosage form
% Preferably 0.0002 to 1% by weight may be contained.

In addition, this substance is administered in doses of 0.1 to ioo, oo per day for adults.
.

p9, preferably 0.5 to 10,000 p9.

Next, we will describe the results of investigating the acute toxicity of this substance.

Acute toxicity: This substance was dissolved in ethanol using 10 ICR male mice (body weight 25 ± 3 (1)), and the ethanol concentration was 2%.
It was dissolved in triglyceride ester of intermediate fatty acid so as to give orally administered (p, o). Dose is 100mM
It is ko. Symptoms of toxicity were observed for 2 weeks after administration, but 1
All of the mice survived without any abnormalities. After slaughter, blood biochemistry search,
Anatomical findings and histopathological examinations revealed no difference from the control group to which only triglyceride ester of intermediate fatty acid containing 2% ethanol was administered. Therefore, the L D so value for oral administration of this substance is 10
Since it is 0 mg/kil1 or more, it can be said to be extremely safe.

The present inventors administered 24R,25-(OH)2-D3 daily to senile or postmenopausal osteoporosis patients with lower back pain.
As a result of oral administration for ~4 weeks, a pain-reducing effect was obtained.

EXAMPLES The effects of the present invention will be specifically explained below with reference to Examples. In addition, 24R,25-(Of-
1) Structure confirmation of the optical isomer at position 24 of -03 is T
etrahedron L etters No
, 26. I)D 2203-2206.1975.

Triglyceride esters of intermediate fatty acids Ik (l
Dissolve 24R,25-(OH)2-D35+no in
0 GC24R,25-(OH)2-D3 in 1 capsule
．． The following shell components were heated and dissolved to contain 5 pg, and soft capsules were prepared in a conventional manner using a soft capsule making machine.

Shell formulation example Gelatin 10 parts by weight Glycerin
2 parts by weight Preservative O, OS parts by weight (ethylparaben) Titanium white 0.2 parts by weight water
0.2 parts by weight (final) Capsules containing 1 gram, 2 gram, 511 g, or 1011 g were prepared in the same manner.

Example 2 24R925-
(OH)2-03 with 1% ethanol vanasate 81
0 to each group for 30 consecutive days. 100.11000Ii/kg・day (7
The results of a comparison of the vehicle-only group and the following items are shown below. According to the growth curve based on body weight measurement, no significant difference in body weight change between groups was observed.

The following organs were fixed with 10% formalin, stained with hematoxylin and eosin, and subjected to histopathological examination, but no particular abnormality was observed.

Brain, heart, lungs, liver, kidneys, adrenal glands, tiles, pancreas, thyroid.

Pituitary gland, thymus, mesenteric lymph, testes, ovaries, uterus.

Stomach, small intestine (jejunum, 9 ileum, duodenum), large intestine (colon).

cecum), eyes, submandibular gland, bladder, back skin, and muscles.

Sternum, thoracic bone marrow, femur, femoral bone marrow.

Blood-membrane test ↑: Increased compared to control Urine test organ mm ↑: Increased compared to control Example 3 Elderly patient with chronic lower back pain and X-ray diagnosis of Jidai bone atrophy grade 1 or above Or 3 to 15 ul of 24R,25-(0H)2 per day for 7 postmenopausal osteoporosis patients.
-D3 was administered daily for 2 to 4 weeks, resulting in lower back pain, gait disturbance, sitting disturbance, [! Observation of subjective and objective symptoms such as sleep disturbances resulted in a score of 14 in the table below. 24R,25-<oH)2-D3 improved or eliminated pain.

Furthermore, as a result of X-ray diagnosis, the patient's previous condition improved.

Continued on page 1 Inventor: Akira Kato 3-1 Nakadai, Itabashi-ku, Tokyo Inventor: Yoshikumi Parents: Kunitachi Ryu 2-19-46, 2
7 K-407 1')AQ-

Claims (2)

[Claims] (1) A pain relief agent for osteoporosis containing 24,25-dihydroxycholecalciferol as an active ingredient. (2) The pain relief agent for osteoporosis according to claim 1, wherein the 24,25-dihydroxycholecalciferol is 24R,25-dihydroxycholecalciferol.