JPH0122A - Preventive/therapeutic agents for hypocalcemia and bone metabolic disorders - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a preventive/therapeutic agent for hypocalcemia and bone metabolic disorders, and more particularly, it relates to a preventive/therapeutic agent for hypocalcemia and bone metabolic disorders, and more specifically, it has no side effects and can be administered over a long period of time. The present invention relates to preventive and therapeutic agents for various diseases caused by calcium deficiency in living tissues, such as bone metabolic disorders such as malacia and osteoporosis.

[Conventional technology]

Calcium exists in the living body as a major component of bones and teeth, and also plays a role in the differentiation and proliferation of cells, secretion of hormones, coagulation of blood, activation of enzymes, stimulus responses of immune cells, nerve transmission, It plays an important role in muscle cell contraction, etc. In order to carry out these functions smoothly, the calcium concentration in the blood is kept constant by the action of the parathyroid hormone and active vitamin D3.

Hypocalcemia is a state in which the blood calcium concentration decreases due to insufficient calcium intake, malabsorption of calcium from the small intestine, imbalance of the regulatory factors, pregnancy, etc. It is one of the causes of tetany symptoms such as excessive excitement of nerves and muscles, spasm of blood vessels and respiratory muscles, osteomalacia, and osteoporosis.

Currently, preventive and therapeutic agents for hypocalcemia and the above-mentioned diseases include calcium preparations such as calcium lactate, calcium carbonate, calcium gluconate, bone/shell powder, and active vitamin Ds (1(1,25-dihydroxyvitamin). D3
) is used.

[Problem that the invention seeks to solve]

These calcium preparations have drawbacks such as poor absorption; poor uptake of calcium into the blood and bones; and difficulty in taking doses due to bad taste and odor.
However, it has the disadvantage of having serious side effects such as loss of appetite, nausea, headache, and delayed fetal bone formation.

[Means for solving problems]

The present inventors conducted extensive research to solve the above problems, and found that hexose calcium phosphate increases blood calcium concentration, has an effect of increasing bone calcium content and bone strength, and has the ability to cause hypocalcemia. and found that it is useful as a prophylactic/therapeutic agent for bone metabolic disorders, and completed the present invention.

That is, the present invention provides a method for preventing and preventing hypocalcemia and bone metabolic disorders using calcium hexose phosphate as an active ingredient.
It provides a therapeutic agent.

Hexose calcium phosphate and Shiteha used in the present invention,
Calcium phosphates of hexoses such as crucose, fructose, mannose, galactose, tagatose, turgose, fucose, kinomese, and rhamnose may be mentioned, and among these, glucose calcium phosphate is preferred. Further, for example, glucose-1-calcium phosphate includes those represented by the following structural formulas (a) or (b) (a) (b), and any of them can be used in the present invention, but in particular ( Those represented by a) are preferred.

The production method of glucose-1-calcium phosphate is shown in Japanese Patent Publication No. 10620/1983 and Japanese Patent Publication No. 23998/1986, and its physiological action is known as caries-preventing effect (Japanese Patent Publication No. 46-1988).
7599), has been reported to have cartilage calcification promoting effects, fatigue recovery effects, etc., but it has also been reported to significantly improve blood calcium levels, have preventive and therapeutic effects on hypocalcemia, and even reduce bone metabolic abnormalities. It is not known to have therapeutic or preventive effects on osteomalacia, osteoporosis, etc.

The preventive/therapeutic agent for hypocalcemia and bone metabolic disorders of the present invention is preferably administered orally, and if necessary, necessary formulation carriers, excipients, etc. are added, and tablets, granules, etc. are prepared by a conventional method. , capsules, oral liquid preparations, etc.

The dosage of this prophylactic/therapeutic agent is 91 to 502 per day for adults.
Preferably it is 10-302.

The acute oral toxicity of glucose-1-calcium phosphate in mice is 15,000'q/K1 or more, making it extremely safe.

〔Effect of the invention〕

The preventive/therapeutic agent for hypocalcemia and bone metabolic disorders of the present invention has good absorption properties and can increase calcium concentration in the blood, and has a high uptake rate into bones, so it can reduce bone calcium content. can be used to increase bone strength and bone strength.

〔Example〕

The present invention will be described in more detail with reference to Examples below, but the present invention is not limited to these Examples.

Example 1 - R star male rats (body weight 250F, -group 10
mice) were fed the low calcium diet shown in Table 1 for 2 weeks. During the rearing period, a glucose-1-calcium phosphate aqueous solution (lf/100-purified water) containing compounds of the structural formulas (a) and (b) in a ratio of 9=l (weight ratio), a structural formula (a
) of glucose-1-calcium phosphate aqueous solution (1?/
100-purified water), calcium lactate aqueous solution (If/Zo
o-purified water) or calcium gluconate aqueous solution (If
/100ttl lfi 1llj water) 1- Each was allowed to drink water ad libitum.

The serum calcium concentration was measured on the day of the end of rearing.

The results are shown in Table 2. As a control, a water intake group was provided on the control diet shown in Table 1.

Table 1 in the margin below Dietary composition (?/Kg diet) Next Harano Q mixture Table 2 Based on the results of Wistar rat serum calcium concentration or higher, the administration of glucose-1-calcium phosphate was
It was found that it increased serum calcium concentration.

Example 2 Comparison of bone strength: Wistar male rats (weight: 2509, 10 animals in the -group) were given glucose-1-
Calcium phosphate aqueous solution (11/100-purified water) and glucose-1-calcium phosphate aqueous solution (1f/100-purified water) containing a compound of structural formula (a), etc. in a ratio of 9=1 (weight ratio)
- purified water) were intragastrically administered for 3.5 d each day for 5 months. On the final day of administration, the femur was removed after decapitation and treated with a fracture property measuring device (DYN-1255 manufactured by Iio Electric) K.
Okay, Shiransha speed 100 m/min
, the chart speed was 1.200 m/min, and the full scale was 25 Kf, and the breaking force was calculated.

As controls, calcium chloride (1f7100dn backwater), calcium lactate (1f/100-purified water), and citrus water administration groups were provided. The results are shown in Table 3.

Table 3 Wistar rat femoral bone fracture characteristics Example 4 Comparison of bone calcium squared: The calcium content of the rat femurs excised in Example 3 was measured.

Accurately weigh 5 ooq of femur, add 5 sd of nitric acid-perchloric acid mixture (4:1) and heat at 80°C for 1 hour, then at 140°C.
It was incinerated for 1 hour. Charel Atush AA-820
The calcium content of the ashed samples was measured on an SFIA Hitachi -1000. The results are shown in Table 4.

Table 4 Wistar Rat Femoral Bone Calcium Content The results of Examples 2 and 3 revealed that administration of glucose-1-calcium phosphate increased bone fracture properties and bone calcium content.

Written amendment to the above procedure (voluntary) April 7, 1988 Kunio Ogawa, Commissioner of the Patent Office,...: ”,1
1ε゛- 1. Indication of the case: Patent Application No. 85436 of 1985 2. Name of the invention: Preventive/therapeutic agent for hypocalcemia and bone metabolic disorders 3.
Relationship with the case of the person making the amendment Applicant name (091) Kao Corporation 4, agent name (6870) Patent attorney Miyuki Ariga, resident
Same as above, Mr. Mi
Name (7756) Patent Attorney Toshio Takano Address Same as above Name (8632) Patent Attorney Nobuo Ono)
& Subject of amendment lfA* "Detailed description of the invention" column 7, Contents of amendment (1) In the specification, page 4, line 5 from the bottom, "notably" was replaced with "notably" I am corrected.

C) On page 5, line 5, ``per day'' should be corrected to ``as hequine calcium phosphate per day.''

(3) Same page 6, line 3 ``I fed him.'' Tooru said, "I fed them (an average of 20 tons per day)," I corrected.

(4) Same amount! @ line 10 ``I made you drink water.'' ``I made him drink water (on average about 30 ounces a day).'' I corrected him.

(5) The bottom line of the same statement, “A water intake group was established for the control diet.” should be changed to “Control diet -
A water intake group and a low calcium diet-water intake group were established. ” he corrected.

(6) Table 2 on page 8 of the same is corrected as follows.

Margin below Table 2 “Quister Rat Serum Calcium Concentration” (7) Same page 9, 2nd line from the bottom "Example 4" Tororu, Corrected to "Example 3".

(8) Bottom row of the same It says "Example 3", Corrected to "Example 2".

Claims (1)

[Claims] 1. A prophylactic and therapeutic agent for hypocalcemia and bone metabolic disorders containing calcium hexose phosphate as an active ingredient.