JPH1036256A - Anti-osteoporosis composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an anti-osteoporosis composition safe in continuous intake, comprising vitamin K2 and zinc as active ingredients. SOLUTION: This composition comprises vitamin K2 and zinc. Vitamin K2 derived from Bacillus natto or Bacillus subtilis is preferable as the vitamin K2 and zinc derived from a food such as dried yeast or bovine bonemeal is used as zinc. The contents of the vitamin K2 and zinc are >=30mg in 1kg solid content, respectively and most preferably >=50mg. By possessing both the vitamin K2 and zinc, a higher bone action is promoted, to adverse effect is found, the composition is effective even with a small intake amount of the vitamin K2 and a nutrient component can also be enhanced.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an anti-osteoporosis composition containing both vitamin K ₂ and zinc as active ingredients.

[0002]

2. Description of the Related Art Osteoporosis is a condition in which bone becomes brittle due to a decrease in bone mass. Osteoporosis not only causes fractures and severe pain, but also causes bedridden especially for elderly people.Therefore, effective treatment methods are required from the viewpoint of improving the quality of life in an aging society. ing.

[0003] Therapeutic agents for osteoporosis include active vitamin D3, female hormones (estrogens), calcitonin,
Ipriflavone is used clinically, and recently, an anti-osteoporosis agent based on the osteoclast formation inhibitory action of a polyisoprenoid derivative represented by vitamin K ₂ (Japanese Patent Laid-Open No. 7-2)
15849) has also been developed.

On the other hand, recently, it is difficult to treat osteoporosis after it has developed, so it is important to work on prevention, and it is essential to increase bone mass from a young age.
It has been deeply recognized that it is necessary to actively take nutritional components necessary for bone formation and foods that promote bone formation on a daily basis. Currently, calcium, magnesium, and vitamin D are mainly used as foods for strengthening bones. Casein phosphopeptides that promote the absorption of calcium from the intestinal tract have also been used. Furthermore, depending on the side chain length, menaquinone (MK)
It is also believed that the use of vitamin K ₂ of the food, which is known as -1～14.

[0005]

However, it has been found that active vitamin D ₃ , a female hormone (estrogen) and calcitonin, which are used as a therapeutic agent for osteoporosis, have side effects and excessive symptoms, which is a problem. Recently, vitamin K ₂ has been used as a safe drug for osteoporosis, but the amount of vitamin K ₂ used for treatment must be as high as 45 mg a day,
In this case, minor, sometimes abdominal pain, nausea, vomiting, rash,
Side effects such as headaches may occur. In addition, the efficacy and safety of ipriflavone when used for a long period of time are unclear. As described above, despite the development of various therapeutic agents for osteoporosis, medication is performed for a long period of time, so that the burden on patients due to side effects and the like is large, and satisfactory therapeutic effects are not necessarily exerted.
On the other hand, the method of reinforcing the bone composition with foods such as calcium does not have a sufficient effect of increasing bone mass or enhancing bone strength.

[0006] In addition, vitamin K _2
2 food Zongai less including more than 1ppm a slightly natto in familiar foods (vitamin K ₂ concentration, several to several tens of ppm) only finds its examples. If you try to ingest a valid vitamin K ₂ in the treatment of osteoporosis by the natto, you must eat several hundred g or more a day natto, there is a preference on the problem. Therefore, attempts have been made to the development of food products with enhanced vitamin K _2. However, like a remedy 45mg a day
When ingested, side effects such as abdominal pain and rash may appear as described above, so that only a smaller amount can be used, but if the amount is reduced, the effect is reduced.

[0007] Exercise is recommended to promote bone formation by applying a load to bones in addition to nutritional guidance. However, in practice, older people tend to have a lack of exercise due to a decrease in physical strength and energy. Is seen. Naturally, exercise alone cannot sufficiently maintain and increase bone mass and bone strength. In recent years, since zinc is contained in a large amount in bone tissue, the relationship between zinc and bone formation has been studied, and the bone formation effect of zinc has been confirmed. Although zinc is widely contained in foods, the average intake for Japanese is 6 to 12 mg, which is insufficient for the recommended intake (15 mg for adults, four revised food composition table 1996, Women's Nutrition University Press). Thus, the bone effects of zinc alone with a normal diet are not desirable. In addition, animal foods and foods containing microorganisms often contain very small amounts of both vitamin K ₂ and zinc, but the effects of these two components on bone are very weak at the amounts contained in the foods. As described above, although there is a demand for the development of a safe functional food having an excellent effect of preventing or treating osteoporosis, a product which has solved both the efficacy and the safety has not been developed at present.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to provide an effective anti-osteoporosis composition which can solve the above-mentioned problems. The present inventors have intensively studied to solve the above-mentioned object. As a result, vitamin K as an active ingredient
By adding ₂ together with zinc, it was discovered that a higher bone augmenting effect was exerted on the metaphyseal tissue of the rat femur, which was raised under no load and had a disorder in bone formation, to prevent osteoporosis or / In addition, it has been found that a more effective anti-osteoporosis composition can be provided by incorporating vitamin K ₂ and zinc together when preparing a functional food or composition for treatment.

Accordingly, the present invention is an anti-osteoporotic composition with enhanced both vitamin K ₂ and zinc. Vitamin K ₂
Zinc that there is but the one is not clear to act in any such mechanism for the bone tissue, probably, osteoclast inhibitory effect of bone formation promoting action and vitamin K ₂ of zinc is thought to work in concert.

[0010]

DETAILED DESCRIPTION OF THE INVENTION Vitamin K used in the present invention_Two 
Can be used for both synthetic and natural products.
When used, those of natural origin are desirable, and
Vitamin K from natto or Bacillus subtilis_Two Is desirable
New Therefore, vitamin K in food _Two Known as
Menaquinone (MK) -1 to 14 can be used
You. Also, vitamin K_Two There is no particular limitation on the manufacturing method of
Min K_Two Dried product of fermented natto bacteria with high content,
Or natto bacteria as it is vitamin K_Two Use as a source
You can also.

The origin of zinc used in the product of the present invention is not particularly limited. In addition to inorganic zinc such as zinc sulfate and zinc chloride, zinc gluconate and the like, natural salts produced from seawater and the like, zinc-binding proteins and peptides Preparations with an increased zinc concentration in foods, such as foods, and foods containing a high concentration of zinc, for example, dried yeast, turmeric powder, dried liver, beef bone meal, oysters, etc. may be used as a zinc source as they are.

When ingesting the composition prepared according to the present invention, the amount of intake varies depending on symptoms, age, etc., but is not particularly limited. However, since the vitamin K ₂ have you intake side effect appears exceeds 45mg, preferably, in the range of less than 45mg in an adult per day 0.05mg above, more desirably,
It is desirable to design the product (composition) so as to be 0.1 mg or more and 10 mg or less. The intake amount of zinc is not limited, but it is generally recommended that the adult be used in an amount of 0.1 mg or more and 10 mg or less per day for an adult.

It is important that the composition according to the present invention contains both vitamin K ₂ and zinc as active ingredients, and minerals such as calcium, magnesium, iron, manganese and copper, vitamin D and vitamin E And vitamins such as ubiquinone, isoflavonoids, flavonoids, peptides such as casein calcium phosphonate, and other normal food ingredients and food additives such as proteins and lipids. In addition, powders, granules, tablets, powders and the like can be prepared using pharmaceutically acceptable carriers, auxiliaries and the like.

Although vitamin K ₂ and zinc may be contained in very small amounts in foods, the anti-osteoporosis agent of the present invention does not contain such a small amount contained in nature but contains 1 kg of solid content. 30mg is the content of vitamin K ₂
(Preferably 40 mg or more, more preferably 50 m
g or more) and the zinc content is preferably 30 mg or more (preferably 40 mg or more, more preferably 50 mg or more). That is, at a concentration lower than this, there is a tendency that a remarkable effect is hard to be exhibited. Next, in order to specifically explain the present invention, examples will be given below, but the present invention is not limited by these. In addition,
The following vitamin K ₂ concentrations were measured by high performance liquid chromatography, and the zinc concentration was measured by atomic absorption.

[0015]

【Example】

Example 1 Powder Material [Formulation] material amount 1) natto extract oil (vitamin K ₂ concentration: 500 ppm) 200 g 2) dry yeast powder (zinc concentration: 150 ppm) 280 g 3) Corn starch 500 g 4) extracted tocopherol 20g above raw materials The powder was mixed with a high-speed mixer to obtain a uniform powder. This powder can be mixed with various foods.

Example 2 Beverage For 1 liter of milk, 0.1 g of vitamin K ₂ (menaquinone-4), 10 mg of zinc sulfate, 0.5 g of cocoa powder, 30 g of sugar, 0.5 g of sucrose fatty acid ester
And vigorously stirred to obtain a cocoa-flavored milk drink.
The obtained beverage has good taste and is easy to drink, so that it can be continuously eaten and consumed daily.

Example 3 Tablets Purified vitamin K ₂ (menaquinone-7, concentration 98%) 20
g was dissolved in 80 g of soybean oil while heating at 50 ° C., and then dextrin powder (Pine Flow, manufactured by Matsutani Chemical Industry)
Vitamin K ₂ powder (A) was prepared by adsorbing on 400 g and powdering. [Formulation] In the raw material mixing amount of vitamin K ₂ powder (A) 50 mg edible bovine bone powder 100mg Lactose 150mg palatinose 30mg zinc gluconate 3mg reduced maltose 10mg Corn starch 10mg cellulose powder 10mg vitamin D3 20 IU (International Units) above blending ratio, the raw materials Was mixed and tableted to give tablets. The resulting tablets have good taste and excellent portability,
It is easy to carry and consume.

[0018]

[Performance test of the present invention]

Test Example 1 Osteoporosis ameliorating effect test [Explanation of Experimental Method] As shown in FIG. 1, the body of a Wistar rat (4 weeks old) 1 was fixed with wires 2 and 2 and no weight was applied to the hind limbs for 4 days. Bred. In this way, bone formation in rat femurs reared in a hindlimb unloaded state is impaired and studied as one of the models of osteoporosis. Thus obtained rat femoral metaphysis part (cancellous bone) cut into small pieces and transferred to 35-mm culture dishes in medium was used to osteoporosis improving effect test of vitamin K ₂ and zinc.

The medium was 2.0 ml of Dulbecco's modified Eagle's medium (glucose concentration 4.5 g / dl) containing 0.25% bovine serum albumin and antibiotics (100 units penicillin and 100 μg streptomycin / ml medium).
It was used. Tissue culture was performed using a CO ₂ incubator at 37 ° C., 5% CO ₂ and 95% in a water-saturated atmosphere.
% Air for 48 hours. Vitamin K ₂ is 99.8% pure menaquinone-7 (MK-7) contained in natto
Purified, dissolved in ethanol, and adjusted to a concentration of 1 mM.

In the medium, natto-derived vitamin K_Two (MK-
7) to 10^-FiveM (final concentration) added, 10^-FiveM
ZnSO_Four Plus 10^-FiveM vitamin K_Two When
10 ^-FiveM ZnSO_Four And control (control
Roll) was tested for 4 conditions with only solvent added,
The amount of calcium in the bone tissue after the culture was compared. Calciu
The amount of calcium is expressed as calcium per dry weight of bone tissue.
Was. Dry weight is to dry the bone tissue at 110 ° C. for 24 hours,
It was measured. The amount of calcium was 120 ° C for dried bone tissue.
Decomposed with 3 ml nitric acid solution for 48 hours
It was measured with a meter.

[Explanation of Experimental Results] Using the metaphyseal tissue of the femur of rats (5 rats) bred under unloaded hind limbs (bone formation is impaired) for 4 days, natural vitamin K ₂ was added to the culture medium.
Table 1 shows the results obtained by adding (menaquinone-7) and zinc singly or as a mixture, and measuring the amount of calcium after 48 hours.

[0022] * p <0.005, ** p <0.01

As shown in Table 1, the addition of vitamin K ₂ alone did not significantly increase the calcium content in bone tissue as compared with the control, whereas the addition of ZnSO ₄ reduced the calcium content. Increased. Thus, vitamin K
Even though the effect does not appear in the ₂ alone ZnSO ₄
When used in combination with ZnSO ₄ , the effect of increasing the amount of calcium in bone tissue was higher than when ZnSO _{4 was} used alone. Vitamin K ₂ for alone may appear one day adult dose 45mg side effects in required to provide a sufficient bone effect, but lesser amount of intake of vitamin K ₂ is desired for osteoporosis prevention According to the present invention, improvement of osteoporosis alone administration of vitamin K _2, even doses as effect does not appear to prevent, by ingesting with zinc,
Vitamin K ₂ and zinc interact, it is apparent that a higher bone effect is promoted. Since the composition of the present invention can be taken daily for preventive purposes from a young age due to its anti-osteoporotic effect without side effects, it not only protects the quality of life of individuals after retirement but also reduces medical costs in an aging society. Can be expected to contribute. At the same time, compositions which can be provided by the present invention, vitamin K ₂ and zinc can ingest simultaneously, it can be carried out also strengthening nutrients.

Test Example 2 Safety Test The acute toxicity test of the powder preparation prepared in Example 1 and the tablet shown in Example 3 was performed by the following method. [Test Method] Male ddy mice of 4 weeks old were grouped in groups of 10
Used. The administration of the test substance is 10 g based on the body weight of the individual.
/ Kg and 5 g / kg were grouped, fasted for 18 hours, and then administered by oral gavage using a magensonde. The mice were bred under conditions of constant temperature and high humidity, and the body weight of each individual was measured while the administration day was 0, and the general symptoms and the state of life and death were observed for 7 days. Water and food were provided ad libitum during this time.

[Test Results] In both the powder preparation (Example 1) and the tablet (Example 3), no fatal cases were observed, and the body weight increased steadily. The appearance was not different from a normal mouse. Therefore, both test substances had an LD ₅₀ of more than 10 g / kg, which proved to be an extremely safe composition. In addition, since vitamin K ₂ and zinc are widely contained in foods, it is determined that they are extremely safe materials with respect to chronic toxicity.

[Brief description of the drawings]

FIG. 1 is a perspective view showing a rearing state of a test rat.

[Explanation of symbols]

 1 rat 2 wires

Claims (5)

[Claims] 1. An anti-osteoporotic composition in which both vitamin K ₂ and zinc are fortified. 2. A composition as in claim 1 wherein the natural vitamin K ₂ vitamin K ₂ is extracted from natural products. 3. The composition according to claim 1, wherein the vitamin K ₂ is derived from Bacillus subtilis or Bacillus natto. 4. The composition according to claim 1, wherein the zinc is derived from food. 5. The composition according to claim 1, wherein the content of vitamin K _{2 in} 1 kg of solid content is 30 mg or more and the content of zinc is 30 mg or more.