JPH0210127B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an antipyretic analgesic agent containing 24,25-dihydroxycholecalciferol as an active ingredient. As a result of intensive research into a substance that is endogenous to the healthy human body and has been proven to be safe, the present inventors discovered 24,25-dihydroxycholecalciferol (hereinafter referred to as this substance or 24,25-dihydroxycholecalciferol). ―
(OH) ₂ -D ₃ ) has been found to have numerous physiologically active effects, and has already shown anti-hypercalcemia,
It has been found to have anti-ulcer effects, prevent immune function decline, regulate magnesium metabolism, anti-hyperphosphatemia, regulate blood sugar, and anti-tumor effects. After that, as a result of repeated research, it was discovered that it has an antipyretic and analgesic effect as described later, and the present invention was achieved. As described below, this substance is a highly safe substance and has an antipyretic analgesic effect, and is useful as a central nervous system depressant, particularly an active ingredient in an antipyretic analgesic. All of these substances are known substances and have the following structures.For example, Anthony W.Norman, Vitamin
D; MOLECULAR BIOLOGY AND
CLINICAL NUTRITION，MARCEL
DEKKER, INC. p. 1-92 (1980). This substance is 24R, 25-(OH) ₂ -D ₃ , 24S, 25-
Although it may be (OH) ₂ --D ₃ or a mixture thereof, 24R,25-(OH) ₂ --D ₃ is particularly preferred. The antipyretic and analgesic agent of the present invention contains the above-mentioned substances as active ingredients, and is used in various formulations as shown below. The antipyretic analgesic of the present invention can be administered orally, parenterally or rectally, but oral administration is 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. Also preferred are cacao oil and glycerin. Other ingredients such as lactose, starch, talc, magnesium stearate, sorbic acid, salts of sorbic acid, sugar or its derivative alcohol, physiological saline, surfactants, antioxidants, or other pharmaceutical agents are used in combination with this substance. It is possible. The substance may be contained in a unit dosage form from 2x10 ^-5 to 4% by weight, preferably 2x10 ^-4 % by weight.
In addition, this substance is administered in doses of 0.1μg to 1x per day for adults.
Administer 10 ⁵ μg, preferably 0.5 to 1×10 ⁴ . Next, we will describe the results of investigating the acute toxicity of this substance. Acute toxicity: The substance was dissolved in ethanol and triglyceride ester of intermediate fatty acids to give an ethanol concentration of 2%, and administered orally (po) to 10 male ICR mice (body weight 25±3 g). . The dose is 100mg/Kg. The animals were observed for symptoms of toxicity for two weeks after administration, but all 10 animals survived without any abnormalities. After slaughter, blood, biochemical tests, autopsy findings, and histopathological examinations were performed, but there was no difference in any way from the control group to which only triglyceride ester of intermediate fatty acid containing 2% ethanol was administered.
Therefore, the LD ₅₀ value for oral administration of this substance is 100g/
1α-(OH)-D ₃ (orally administered), which is said to be an active vitamin D ₃ analogue.
(LD ₅₀ is less than 1 mg/Kg), this substance can be said to be extremely safe. EXAMPLES The effects of the present invention will be specifically explained below with reference to Examples. In addition, this substance used in the examples is
24R,25-(OH) ₂ - _D3 , and the structure of the optical isomer at position 24 was confirmed in Tetrahedron Letters No.
26, p. 2203-2206, 1975. Example 1 Antipyretic and analgesic effect (1-1) Analgesic effect mechanical stimulation method (pressure stimulation method) Takagi, Kameyama et al.'s pressure stimulation device (manufactured by Natsume Seisakusho)
The test animal was an ICR mouse (♀), and pressure was applied to the ridge of the mouse until the pain threshold was 50.
Those exhibiting ~80 mmHg were selected and each group consisted of 10 animals. After oral administration of 100 μg/Kg of this substance dissolved in MCT (triglyceride ester of C ₈ to _{C 10} carboxylic acids), measurements were taken over time to determine the pressure and required pressure up to the point at which the test animal showed a pseudoescape response. The time (seconds) was measured, and the analgesic effect was determined based on the pressure and the required time. Chemical stimulation method ICR mice, 5-6 week old (♀) mice
A group of 10 animals was prepared, and 6 hours after oral administration of 100 μg/kg of this substance dissolved in MCT, 0.1 ml/kg of 0.6% acetic acid solution was administered according to the method of Kostet et al (1959).
After 10 minutes of intraperitoneal injection per 10 g of mouse body weight, the number of writings that occur in the mouse was counted, and the inhibition rate (%) compared to the control group was calculated using the following formula:
I asked for The control group was a group administered only with MCT. (1-T/C)×100=IR (%) T: Average number of writings in the administration group C: Average number of writings in the control group The results are shown in Table 1 below.

[Table] (1-2) Antipyretic effect According to the method of Winter et al (1961), group 16
A 20% brewer's yeast suspension was subcutaneously administered to rats, and after fasting for 19 hours, the substance dissolved in MCT was administered subcutaneously to rats.
Orally administered 100 μg/Kg, measured rectal temperature,
The fever suppression rate with respect to the control fever rat body temperature at the maximum effect of the sample was calculated from the following formula:
The fever suppression rate was 36.8%. C ₁ - T / C ₁ - C ₂ × 100 = IR (%) T: Average body temperature of the administration group C ₁ : Average body temperature of control fever rats C ₂ : Average body temperature of control untreated rats It is found to be advantageous as an antipyretic analgesic. Example 2 Peroxide was removed by irradiation with a 400W high-pressure mercury lamp for 72 hours while bubbling argon.
24R, 25- (OH) ₂ - for 1 kg of removed MCT
Dissolve 5mg of _D3 , 24R, 25-
The following shell components were heated and dissolved so as to contain 0.5 μg of (OH) ₂ -D ₃ , and soft capsules were prepared by a conventional method using a soft capsule making machine. Shell formulation example Gelatin 10 parts by weight Glycerin 2 parts by weight Preservative (ethylparaben) 0.05 parts by weight Titanium white 0.2 parts by weight Water 0.2 parts by weight (parts by weight in final form) Similarly, 1 μg, 2 μg, 5μg
Alternatively, one containing 10 μg was prepared.

Claims (1)

[Scope of Claims] 1. An antipyretic analgesic agent containing 24,25-dihydroxycholecalciferol as an active ingredient. 2. The antipyretic analgesic agent according to claim 1, wherein the 24,25-dihydroxycholecalciferol is 24R,25-dihydroxycholecalciferol.