JPS60120812A - Remedy for diabetic osteopenia - Google Patents

Abstract

PURPOSE:A pharmaceutical, containing active vitamin D3 such as 1alpha-hydroxycholecalciferol, 1alpha-24-dihydroxycholecalciferol, etc. as an active constituent, and very useful for treating diabetic osteopenia. CONSTITUTION:A remedy for diabetic osteopenia containing active vitamin D3 such as 1alpha-hydroxycholecalciferol, 1alpha-24-dihydroxycholecalciferol, etc. in an amount of 0.1-10mug. The administration of the active vitamin D3 remarkably increases the mineral content in bones of a patient with a diabetic osteopenia, e.g. osteoporosis or osteomalacia, as compared with a patient suffering from usual osteopenia and therefore is very useful for treatment. The above-mentioned remedy is preferably in the form of oral administation, e.g. gelatin soft capsule.

Description

[Detailed description of the invention] The present invention relates to a therapeutic agent for diabetic osteopenia.

More specifically, the present invention relates to a therapeutic agent for diabetic osteopenia containing active vitamin D such as la-human ρ xycholecalciferol, IF, and 24-dihydroxycholecalciferul as an active ingredient. .

1α-hydroxycholecalciferol, la.

24-dihydroxycholecalciferul, 1α.

The active form of vitamin D in 25-dihydroxycholecalcifernato regulates calcium levels in the body,
It is known to be useful for so-called osteopenias such as osteoporosis and osteomalacia (U, S, Pat*r+t N
o, 4.022.891 ; Vitamin D (VItami
nD) :Basic Research 7n Germany! Clinical application (Ba5icR*++ear
ch and Its cllnical Appli
(1979) 1099-1106).

On the other hand, in recent years, attention has been paid to the relationship between active vitamin D and insulin levels in the body, and many reports have been made regarding this.

Among these, especially the literature (endocrinology (Kn
docrlnology), vol108, No.
2, 733-735. 1981j K conducted an experiment using chickens and found that insulin
It has been described that 4-promoting enzymes of α,25-dihydroxycholecalciferol, which is a metabolite of vitamin D, have been described. Literature “Science (SC+I B NCE)
), vo1209, 823-825 (1980)
J. conducted perfusion experiments on rats and reported that vitamin D+ promotes insulin secretion from the viscera, while having no effect on glucagon secretion.

In addition, Reference 1: Research, Communication, Chemical Barthology and Pharmacology (Re5)
eareh Comrnunicatlons InC
Chemical Pathology and Pha
rmacology), vol.

33, Nol, JυIy, 15s~161 (19
81) J used genetically obese mice with abnormally high plasma glucose and insulin levels. By administering 1α-hydroxyflecalciferol to these mice, plasma glucose and insulin levels were reduced. levels returned to normal, while calcium levels were shown to be unaffected, suggesting that 1α-hydroxyflecalciferol increases the M&S sensitivity of insulin receptors present in the body. There is a statement to that effect.

However, to the best of the present inventor's knowledge, active vitamin D, such as lα-hydroxyflecalciferol and lα,24-dihydroxycholecalciferol, are effective in diabetic conditions caused by decreased insulin levels.
There is no literature reporting on the effect of K on bones in vivo.

The present inventors have demonstrated that when active vitamin Dsai such as 1a-hydroxycholecalciferol and 1α,24-dihydroxycholecalciferol are administered to patients with diabetic osteopenia, which is known as a complication of diabetes, ,
As a result of detailed consideration of the impact,
The administration of active vitamin D significantly increases the mineral content in the bones of patients with diabetic osteopenia compared to administration to normal osteopenic patients. The present invention was achieved by discovering that vitamin Das are particularly useful in the treatment of diabetic osteopenia.

Therefore, the present invention is a therapeutic agent for diabetic osteopenia containing active vitamins US as an active ingredient.

Examples of active vitamin Ds used in the present invention include 1α hydroxycholecalciferol, Ia
, 24-dihydroxycholecalciferol, 1α, 2
5-dihydroxycholecalciferol, 1α, 2'4
．． 25-9-do-pxiflecalciferol, 1αl
24-dihydroxyfrecalciferul is preferred.

These active vitamin D types are known compounds,
For example, the Journal of the American Chemical Society (
J, Am, Chem, Soe, ), 95.274
8 (1!173); Chemical Pharmacological Bulletin (Chem, Pharm, Boll),
21.2568 (1978); U, 8. Patant4
．． It can be easily chemically synthesized by the method described in 022.891.

Such active forms of vitamin D, when administered to patients with diabetic osteopenia, increase the mineral content in the bones of
The amount increases significantly compared to when administered to normal osteopenic patients. Therefore, drugs containing active vitamin D, @, as an active ingredient are extremely effective in treating diabetic osteopenia.

In the present invention, 1° diabetic osteopenia refers to a pathological condition in which so-called osteopenia such as osteoporosis and osteomalacia occurs due to diabetes.

Active vitamin D may be administered either orally or parenterally, and parenterally, intramuscularly.

Examples include subcutaneous, intravenous, and rectal administration. Among these, oral administration is preferred, and therefore the therapeutic agent of the present invention is preferably in an oral dosage form. An example of a dosage form of a therapeutic agent for diabetic osteopenia containing active vitamin D as an active ingredient is a capsule/L preparation.

Tablets, powders, granules, suppositories, alcohol solutions.

Examples include oil solutions and aqueous suspensions. As for capsules, gelatin soft capsules are preferred.

As a solvent for the oily solution, vegetable oils such as coconut oil, corn oil, cottonseed oil, coconut oil, peanut oil, fish liver oil, oily esters such as polysorbate 80, etc. can be used.

Ingredients, powders, granules, etc. contain lactose and starch.

Suppositories are manufactured by known methods using conventional compounds such as talc, magnesium stearate, sugar, etc. Suppositories are obtained by conventional methods from cocoa butter or its triglycerides.

Furthermore, in order to extend the shelf life of active vitamin Ds, it is advantageous to incorporate antioxidants such as sulfuric acid, dithylated hydroxyanisole or hydroquinone into the droplet. In addition, for the purpose of stabilizing the preparation, active vitamin D and #A can be used as an inclusion compound with β-cyclodextrin or methylated ikptextrin.

The dosage of active vitamin D is 0.0002 to 1 pt.
kZ day, preferably 0.002-0.2 pt/h/
The range of days is 1-1. Therefore, the preparation of the present invention preferably contains 0.1 to 10 μ2 of active vitamin D as an active ingredient.

As detailed above, according to the present invention, there is provided a therapeutic agent for diabetic osteopenia containing active vitamin D as an active ingredient. , is extremely useful in the treatment of pathological conditions accompanied by so-called osteopenia such as osteomalacia.

Hereinafter, the present invention will be explained in more detail with reference to examples. I will clarify.

Example 1 (i) A clinical trial was conducted on 98 geriatric women aged 92 to 92 years old, who were classified into the following groups.

Group 1, patients with diabetic osteopenia who were not given active vitamin D: Thirty-two elderly women with diabetes were treated with diabetes control, and their bone mineral content (t) decreased over two years. Content (aMc) was measured over time.

Patients: Changes in bone mineral content over time were measured for 2 years without treatment for 20 osteopenic patients.

1α-Hydroxycholecarfer 1 pf/day was administered to 7 patients with diabetic osteopenia for 2 years, and changes over time in bone mineral content were measured.

Animals with osteoporosis treated with 1α-hydroxycholecalciferol 0.5 to 1 μW/day to 10 patients with osteopenia.
The drug was administered over a period of one year to examine changes in bone mineral content over time.

1α for 11 patients with diabetic osteopenia.

24-dihydroxyconcalciferol ip! ///
day was administered for two years, and the bone mineral content was examined.

Group 6, lα,24-dihydroxycholecalciferol, 1 μft'/day, was administered to 18 osteopenic patients for 2 years, and changes over time in bone mineral content were investigated.

(11) Here, the method for measuring bone mineral content is a well-known method, and is photo-oaba psiometry.
(ortiometry). RMC's tears are intoxicated after treatment, 3 months, 6 months, 12 months after treatment,
It was carried out at 18 months and 24 months.

The bone mineral content (CRMC) before treatment was taken as 100%, and subsequent values were expressed as changes from the pre-treatment value.

As a general rule, for the past year, diabetic patients' antidiabetic drugs have been varied to maintain good diabetes control, and their diet has been limited to 1,200 to 1,800 Kd per day. The measurement results of the change in salt content over time are shown in FIGS. 1 and 2.

(,) The following can be seen from Figure 1.

The first group does not administer active vitamin D1.

In the second group, bone mineral content decreased, and lα-hydroxycholecalciferul was administered to N? ,: In the case of the fourth group (osteoporosis patients), the bone mineral content does not decrease.

On the other hand, in the case of the third group in which 1α-hydroxycholecalciferol was administered to diabetic osteopenia patients, the bone mineral content significantly increased. From this, it is recognized that lα-hydroxycholecalciferol is particularly useful for treating patients with urinary osteopenia.

(b) The following can be seen from the M2 diagram.

The first group does not administer active vitamin D.

In the second group, bone mineral loss is reduced. On the other hand, 1α, 24
- Bone mineral content increases in the fifth and sixth groups to which dihydroxyl cholecarferul was administered. Also, when comparing Group W (diabetic osteoporosis, @'4') and Group 6 (osteoporotic patients), the bone mineral content in Group 5 increased by 4? L
Therefore, 1α,24-dihydroxycholecalcifer 11-al is recognized to be particularly useful for the treatment of diabetic osteopenia patients.

Example 2 Gelatin 1, in which 1α-hydroxycholecalciferol was dissolved in fatty oil to obtain an oily solution with a concentration of 7' pt/-
00 parts by weight, glycerin 20 parts by weight.

0.2 parts by weight of ethyl paraoxybenzoate, 0.2 parts by weight of bupyl nokuraoxybenzoate, 0.5 parts by weight of 1-para-sulfophenylazo-2-naphthol-6-sulfonic acid disodium salt A shell composition consisting of 80 parts by weight of water and 80 parts by weight of purified water was heat-dissolved to prepare a stock agent, and the shell was made using a continuous soft capsule manufacturing machine so that each capsule contained lpv of la hydroxycholecarferol. gelatin soft capsules were prepared.

[Brief explanation of the drawing]

Figure 1 shows the bone mineral content i (11 Mc
) and changes in bone mineral content in other cases. Figure 2 shows the bone mineral content when 1α,24-di-droxycholecalciferul is administered to patients with diabetic osteopenia.
(RMC) and changes in bone mineral content compared to other cases. In FIGS. 1 and 2, the numbers in parentheses indicate the number of examples.

Claims (1)

[Scope of Claims] 1. A therapeutic agent for diabetic osteopenia containing active vitamin D and the like as an active ingredient. 2. The therapeutic agent for diabetic osteopenia according to claim 1, wherein the active vitamin DaFA is 1a-hydroxycholecalciferul. A therapeutic agent for diabetic osteopenia. 4. The therapeutic agent for diabetic osteopenia according to any one of claims 1 to 3, containing 0.1 to 10 μf of active vitamin D. 5. Claims 1 to 4 in oral dosage form
6. The therapeutic agent for diabetic osteopenia according to claim 5, wherein the oral administration form is a gelatin soft capsule.