JPS63166829A - Agent for increasing bone strength - Google Patents

Abstract

PURPOSE:To obtain an agent to be administered to a healthy person to increase the bone strength and having high safety, by using a 24,25- dihydroxycholecalciferol as an active component. CONSTITUTION:The objective agent can be produced by mixing a 24,25- dihydroxycholecalciferol, preferably 24R,25-dihydroxycholecalciferol properly in an oily solvent, lactose, starch, talc, sorbic acid, an alcohol, physiological salt solution, a surfactant, an antioxidant, etc., and forming to a form of a drug by conventional method. It can be used in the form of tablet, powdery, granule, suppository, capsule, alcoholic solution, aqueous dispersion, etc. The content of the active component in the drug is 0.00002-4wt.% and the component is administered at a dose of 0.1-100,000mug, preferably 0.5-10,000mug daily for adult.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention consists of 24. The present invention relates to a bone strength enhancer containing 25-dihydro-4-cicholecalciferol as an active ingredient.

With the advent of the so-called aging society in recent years, even normal people who do not have bone metabolic diseases tend to physiologically lose bone strength as they reach old age, making them more susceptible to fractures due to minor external forces compared to their prime age. The number of elderly people who are dying is steadily increasing. In the elderly, once a fracture occurs, the progression of inactive bone atrophy accelerates, and increasing bone strength is an extremely important issue.The development of drugs that can improve bone strength is expected. has been done.

As a result of intensive research into substances that are endogenous to the healthy human body and have been proven to be safe, the inventors have found that 24. 25-dihydro “]xy” lecalciferol (hereinafter referred to as this substance or 24.25-(OH)-03
), but there are many 11! ] I have already found that it has an active effect, and regarding bones, bone metabolism! I! It has been found that it has an anti-coagulant effect on 11-propagation, which is one of the common symptoms. Subsequently, as a result of aborted ωl research, it was discovered that administration of this substance to normal animals enhances bone strength greater than that of normal animals, resulting in the present invention. J3 Conventional bone metabolism regulators have only been approved for use in restoring bones that have become abnormal due to pathological conditions to near normal levels, so the current findings are positive.

This substance is a known substance and has the following structure, for example, as disclosed in Pharmacia, Rev., 319-322 (1974).

24t25-(OH)2-0324R,25-(0H)
2-D324S, 25-(0H)2-D3 This substance is 24R,25-(O)-1) 2-03.24
S.

25-(Ol-1) 2- o3 or a mixture thereof), but especially 24R,25-(OH) 2-
D3 is preferred. The pipe strength enhancer of the present invention contains the above substances as active ingredients and is used in various formulations as shown below. The painless IJ of the present invention! The potentiator is administered parenterally, such as intraperitoneally, but may also be administered casually.

Preparations containing this substance as an active ingredient include tablets, RLLs, granules, suppositories, capsules, alcoholic solutions, oily solutions,
It is used in dosage forms such as aqueous suspensions. As the oily solvent, triglyceride esters of intermediate fatty acids, corn ura, cottonseed oil, peanut oil, fish liver oil, oily esters, etc. are used. Also preferred are Chiriki A oil, Glyrin, and the like. Other ingredients include lactose, starch, talc, magnesium stearate, sorbic acid, salts of sorbic acid, sugar or derivatives, alcohol, physiological saline, surfactant 9M
Antioxidants, etc. may be used in combination with this substance.

The substance may contain from 0.00002 to 4% by weight, preferably from 0.0002 to 1 fff, 1M% in the medium dosage form.

In addition, this substance has a dosage of 0.1 to 100.00 per day for adults.
0 p9, preferably 0.5 to 10,000 p9.

Next, we will describe the results of investigating the easy-going nature of this substance.

Acute toxicity: Using 10 ICR male mice (body weight 25 ± 3 g), this substance was dissolved in ethanol, dissolved in the intermediate fatty acid triglyceride nisdel so that the ethanol concentration was 2%, and administered orally (p, o) Administered. The interval between doses is 9 in 100 η/. After administration, symptoms were observed for 2 weeks, but 10
Both animals survived without abnormalities, and after sacrifice, blood biochemistry examination, 1 finding of seal, and histopathological examination were performed. There was nothing that would change. Therefore, the D5o value for oral administration of this substance is 100η
/Kg or more, so it can be said to be extremely safe.

The effects of the present invention will be specifically explained below using examples. In addition, 24R,25-(OH) used in the examples
-The structure of the optical isomer at position 24 of D3 is confirmed by Tetr
ahedron Letters No. 26, DI)
2203-220J1975.

Example 1 1 with 400W high pressure mercury lamp in argon bubbling
2 kg of triglyceride esters of intermediate fatty acids were irradiated for 2 hours to eliminate impure reactive peroxides.
4R, 25-(01]) -D35#I! 24R, 25-(01-1), 2- in one capsule.
The following shell components were heated and dissolved so as to contain 0.5 g of D3, and soft capsules were prepared by a conventional method using a soft capsule making machine.

Shell formulation example Gelatin 10 1M parts Glycerin 2 parts by weight Preservative (ethylparaben > O, OS heavy R part Titanium white
0.2 parts by weight water
0.2 parts by weight (parts by weight in the final form) In the same manner, 1 capsule, 2 grams, 5p9, or 10119 containing b were prepared, respectively.

Example 2 24 [<.

25 (OH) 2 D3 was dissolved in Banahito 810 containing 1% ethanol at a predetermined concentration, and 10 and 100.1000 I was added to each F and T, respectively, for 30 consecutive days.
J! The results of a comparison of I/l (forced orally administered by g/l by hanging, with solvent only l! No difference of $1 in right breath was observed.

Urine test ↓: Decreased compared to the control →; No change compared to the control ↑: Increased compared to the control After fixing the organ with 10% formalin, it was stained with hematopoietic 4-syrin and 1,4-sin, and a histopathological examination was performed, but no particular abnormality was found.

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

Pituitary gland, thymus, piA interstitial lymph, testis, ovary, uterus.

Helmet, small intestine (1 time in the sky, 12 fingers), large intestine (colon).

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

Breast 15 (, thoracic bone marrow, femur, femoral bone marrow.

Example 3 (Method) After preliminarily breeding male Wistar rats (4) withdrew for 2 weeks, the femurs of old rats to which 24R,25-(OH)2-o3 had been orally administered for 24 months were harvested. Iio Electric's former IEODYNACOIID [R, ItDn-1500
(D) Using (full scale/2ONgo-docel), the distance between the fulcrums is $11113. ．． 6.5 from the lesser trochanter
It was broken at the rIuR point and the breaking force was measured.
l-1)-D3 was uniformly dispersed in glycine, and mixed in GE-2 manufactured by Nippon Talea so that the glycine content was 0.5 weight and 7 fi%, the amount of food consumed was measured, and the dosage was calculated.

(Result) A typical measurement chart is shown in FIG.

[Brief explanation of the drawing]

Figure 1 shows the agent for the administration group of the substance of the present invention described in Example 3, Itaru Nakamura, Procedural Amendment No. 1, November 10, 1988, Case Indication, Special Revised Application No. 309393 of 1988.
May 2, Title of invention Pipe strength enhancer 3, Amendment related to 16-party case Patent applicant name (110) Kureha Chemical Industry Co., Ltd. 4, Agent Yamada Building, 1-1-14 Shinjuku, Shinjuku-ku, Tokyo 8. Contents of amendment (1) In the specification, between page 6, line 10 and line 11: [This substance is useful for normal animals, especially normal humans. ” is inserted. ■ In the specification, page 6, line 14 1] [pp 2203
j is corrected to rp, 2203 J. () In the specification, on page 14, line 1, “strength measurement [・
- Correct "to" with "strong measurement chart". C) Amend the attached drawings as shown in the attached sheet.

Claims (2)

[Claims] (1) A normally used bone strength enhancer characterized by containing 24,25-dihydroxycholecalciferol as an active ingredient. (2) The bone strength enhancing agent according to claim 1, wherein the 24,25-dihydroxycholecalciferol is 24R,25-dihydroxycholecalciferol.