JP2014001201A - Agent for prevention and/or improvement of osteoporosis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an active ingredient which can notably exert an effect of preventing and/or improving osteoporosis, and which can be used in food or beverages.SOLUTION: The present invention provides: an agent for prevention and/or improvement of osteoporosis and an agent for prevention and/or improvement of decrease in bone ratio containing an ascorbic acid derivative as an active ingredient; and food or beverages containing an agent for prevention and/or improvement of osteoporosis or an agent for prevention and/or improvement of decrease in bone ratio.

Description

  The present invention relates to an agent for preventing and / or improving osteoporosis.

  In recent years, with the advancement of science and the improvement of living standards, the lifespan of mankind has increased. As the elderly population increases, osteoporosis continues to increase year by year. Currently, the number of osteoporosis patients is said to be 4-5 million. Among them, postmenopausal osteoporosis, which is classified as primary osteoporosis, frequently occurs in women over the age of 50, and accounts for 90% or more of the number of osteoporosis patients. For this reason, osteoporosis is a disease that is regarded as important in modern society, like lifestyle-related diseases represented by diabetes. In addition, there is a risk of causing dementia if the lumbar spine or femur is broken due to osteoporosis and the bedridden state is prolonged. Therefore, prevention of osteoporosis and early development of therapeutic drugs or foods are desired for the purpose of comprehensive improvement of QOL (Quality of life).

  Osteoporosis is a systemic bone disease that causes a decrease in bone mass due to a decrease in components such as calcium and collagen that form bone (mainly cancellous bone) and a regression of the fine structure of bone tissue, causing bone pain It is characterized by bone fragility and risk of fracture. In the onset of osteoporosis, many factors are considered to be directly or indirectly involved in multiple ways. Such factors have been reported such as decreased estrogen secretion due to menopause, calcium metabolism-regulating hormone, nutritional factors such as calcium intake, moderate exercise and mechanical stress such as gravity. These factors are thought to be involved in each other in complex ways and affect bone metabolism.

  Human bones are constantly resorbing and remodeling. The cells that play a central role in the bone metabolism process are osteoblasts responsible for bone formation and osteoclasts responsible for bone resorption. It has been confirmed that the number of osteoblasts decreases with aging. Bone tissue growth, maintenance, and repair depend on a balance between bone formation rate and bone resorption rate. If this balance is lost and calcification is reduced, bone resorption exceeds bone formation and bone mass decreases. However, diseases such as osteoporosis are brought about.

  As therapeutic agents for osteoporosis, calcium, active vitamin D3, estrogen, calcitonin, ipriflavone, vitamin K2, and bisphosphonate related compounds are used. In addition, calcium and vitamin D are mainly used as foods for strengthening bones, and isoflavonoids such as genistin are being used recently.

  L-ascorbic acid is known to be important for the synthesis of collagen in vivo, which is a major component of the bone matrix. That is, L-ascorbic acid is essential for the biosynthesis of hydroxyproline and hydroxylysine, which are amino acids specific to collagen. For example, when added to an osteoblast culture system, collagen synthesis is promoted and osteoblast differentiation. It is known to promote bone formation.

  L-ascorbic acid has a drawback that it easily undergoes oxidative degradation and easily loses its physiological activity. Therefore, as a method for stabilizing L-ascorbic acid, L-ascorbic acid derivatives such as sugar derivatives and ester derivatives have been proposed. Non-Patent Document 1 discloses that the stability of L-ascorbic acid phosphate ester is higher than that of L-ascorbic acid, and that L-ascorbic acid 2-phosphate ester promotes proliferation and differentiation of cultured osteoblasts. It is described as having an effect.

  It is known that diabetics are prone to fractures, and the detailed cause is still unclear. In osteoporosis associated with menopause and the like, bone density (BMD: bone mineral density) decreases due to the promotion of bone resorption function, whereas in osteoporosis due to diabetes, bone density (BMD: bone mineral density) does not decrease. It has been reported that the cause and symptoms of both are different. An effective preventive and / or ameliorating agent for fractures caused by obesity and diabetes is not known. In addition, bisphosphonate (bone resorption inhibitor), which is a typical prophylactic and therapeutic agent for osteoporosis associated with menopause and the like, has an effect of improving BMD, and therefore is not expected to be effective for fractures caused by diabetes.

Cell Biol Int. 2004; 28 (4): 255-65.

  None of the conventional drugs for treating osteoporosis have satisfactory therapeutic effects. In particular, calcium preparations require a very large intake in order to obtain an effect. Side effects were also a problem as described below. Calcitonin is susceptible to drug resistance and cannot be administered orally. Active vitamin D3 tends to cause hypercalcemia. Bisphosphonate related compounds inhibit bone formation. Side effects such as flushing of the face, breast pain, and genital bleeding from the uterus and vagina frequently occur during long-term administration of estrogen preparations over 6 months. These therapeutic agents are administered only after diagnosis of osteoporosis, and are not a preventive measure for osteoporosis. Furthermore, the purchase of an osteoporosis treatment leads to high medical costs for the patient.

  Furthermore, there are currently no known pharmaceuticals or foods that prevent, suppress or ameliorate osteoporosis due to diabetes.

  Further, conventional foods that strengthen bones have not been effective in preventing osteoporosis. If an effect of preventing osteoporosis is to be exhibited, it is necessary to add a large amount of the active ingredient alone to the food, which cannot be used as a food material, and causes a decrease in food preference.

  The object of the present invention is to provide an active ingredient that can remarkably exhibit the effect of preventing and / or improving osteoporosis and can be used as a food or drink.

  When the present inventors conducted the test which administers the derivative | guide_body of L-ascorbic acid to an animal, it discovered that the bone density of cancellous bone increased notably. Further, the present inventors have found that the bone ratio (BV / TV) is decreased in the diabetes model mouse, and that this decrease in BV / TV is suppressed when an ascorbic acid derivative is administered. From these findings, the derivative of L-ascorbic acid is useful as an active ingredient of various osteoporosis prevention and / or improvement agents including osteoporosis caused by diabetes, and as a preventive and / or improvement agent for bone ratio reduction. The conclusion was reached that the present invention has been reached.

The present invention provides the following inventions.
[1] An agent for preventing and / or improving osteoporosis comprising an ascorbic acid derivative as an active ingredient.
[2] The agent for preventing and / or improving osteoporosis according to the above [1], wherein the ascorbic acid derivative is ascorbic acid phosphate magnesium salt and / or ascorbic acid-2-glucoside.
[3] The osteoporosis preventing and / or improving agent according to the above [1] or [2], wherein the osteoporosis is osteoporosis due to diabetes.
[4] A preventive and / or ameliorating agent for reducing bone ratio, comprising an ascorbic acid derivative as an active ingredient.
[5] The preventive and / or ameliorating agent according to the above [4], wherein the ascorbic acid derivative is an ascorbic acid phosphate magnesium salt.
[6] From the osteoporosis prevention and / or improvement agent according to any one of [1] to [3] above, and the bone ratio reduction prevention and / or improvement agent according to [4] or [5] above A food or drink containing one or more agents selected from the group consisting of:

  According to the present invention, osteoporosis and fractures can be prevented in advance, these risks can be reduced, and symptoms can be improved after the onset of osteoporosis.

FIG. 1 is a graph showing the volume of the void portion of cancellous bone in Example 1 (APM administration) and Comparative Example 1 (DW administration). FIG. 2 is a cross-sectional view of cancellous bone in Example 1 (APM administration), Example 2 (A2G administration), and Comparative Example 1 (DW administration). FIG. 3 is a cross-sectional view of cancellous bone of Comparative Example 2 (healthy mouse). FIG. 4 is a graph showing BMD of Example 1 (APM administration), Comparative Example 1 (DW administration), and Comparative Example 2 (healthy mouse). FIG. 5 is a graph showing BV / TV of Example 3 (APM administration), Comparative Example 3 (DW administration), and Comparative Example 4 (healthy mouse). FIG. 6 is a sectional view of a molar tooth of Example 3 (APM administration). FIG. 7 is a cross-sectional view of a molar tooth of Comparative Example 3 (DW administration). FIG. 8 is a sectional view of the molar teeth of Comparative Example 4 (healthy mouse).

  The active ingredient in the present invention is an ascorbic acid derivative. Ascorbic acid derivatives include a part of ascorbic acid ((R) -3,4-dihydroxy-5-((S) -1,2-dihydroxyethyl) furan-2 (5H) -one, vitamin C) A compound obtained by substituting with an atom or a substituent of Ascorbic acid, which is the base of the ascorbic acid derivative, may be any of D-form, L-form, and DL-form, but is preferably L-form. The ascorbic acid derivative is not particularly limited as long as it can be used in the fields of pharmaceuticals, quasi drugs, cosmetics, and foods. Examples include ester derivatives of ascorbic acid or salts thereof, ether derivatives of ascorbic acid or salts thereof, and salts of ascorbic acid.

  Examples of ester derivatives of ascorbic acid include esters of ascorbic acid and acids such as carboxylic acid, sulfuric acid, sulfonic acid, and phosphoric acid. As an esterification site | part of ascorbic acid, each hydroxyl group of 2nd-position, 3-position, 5-position, and 6-position of ascorbic acid is mentioned, for example. In the ester derivative of ascorbic acid, the number of ascorbic acid esterification sites may be one or more, and one or more hydroxy groups selected from the above hydroxy groups may be esterified. When the number of esterification sites is 2 or more, the type of acid forming the ester may be the same or different at each esterification site.

  Examples of the carboxylic acid include aliphatic carboxylic acids and aromatic carboxylic acids.

  Examples of the sulfonic acid include sulfonic acid and alkylsulfonic acid. The alkylsulfonic acid is usually an alkylsulfonic acid having 1 to 6 carbon atoms, and examples thereof include methylsulfonic acid and ethylsulfonic acid.

  Examples of phosphoric acid include phosphoric acid, phosphoric acid monoester, and phosphoric acid diester, and the details are as follows: phosphoric acid; monoalkyl ester of phosphoric acid (for example, one hydrogen contained in phosphoric acid, An alkyl group selected from alkyl groups having 1 to 6 carbon atoms such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, s-butyl group, t-butyl group, isobutyl group, pentyl group and hexyl group; Substituted monoesters of phosphoric acid; dialkyl esters of phosphoric acid (eg, the two hydrogens of phosphoric acid are methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl) Dialkyl group of phosphoric acid substituted with two alkyl groups selected from alkyl groups having 1 to 6 carbon atoms such as a group, isobutyl group, pentyl group, hexyl group, etc. Tel etc.) and the like. In the phosphoric acid dialkyl ester, the two alkyl groups may be the same or different from each other.

  Examples of ether derivatives of ascorbic acid include ascorbic acid glucoside (eg, ascorbic acid-2-glucoside).

  The ascorbic acid derivative may be a salt of ascorbic acid or a salt of ascorbic acid derivative. Examples of the salt include the following salts: various metal salts such as alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium, calcium and barium, and polyvalent metal salts such as aluminum; ammonium, Ammonium salts such as tricyclohexylammonium; various alkanolamine salts such as monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine;

  Ascorbic acid derivatives preferably used in the present invention include L-ascorbic acid salts (for example, sodium salts), L-ascorbic acid phosphoric acid ester derivatives (for example, L-ascorbic acid monophosphate sodium salt, phosphoric acid L -Ascorbyl magnesium (ascorbic acid phosphate ester magnesium salt (APM) and the like) and salts thereof, Ascorbic acid glucoside (eg ascorbic acid-2-glucoside and the like) and salts thereof, Ascorbyl tetraisopalmitate (VCIP) and salts thereof Ascorbic acid-2-phosphate-6-palmitate (APPS) and salts thereof, and more preferably used ascorbic acid derivatives are sodium L-ascorbate, magnesium L-ascorbyl phosphate, ascorb Acid 2-glucoside (for example, ascorbic acid-2-O-α-glucoside), and more preferably used ascorbic acid derivatives include L-ascorbyl magnesium phosphate, ascorbic acid-2-glucoside (for example, ascorbic acid) -2-O-α-glucoside (A2G)).

  As the ascorbic acid derivative, one artificially synthesized by chemical synthesis or the like may be used, or a commercially available product may be used.

  The ascorbic acid derivative as an active ingredient in the present invention may be one kind or a combination of two or more kinds.

  The blending amount of the ascorbic acid derivative in the osteoporosis prevention and / or amelioration agent of the present invention is not particularly limited as long as it is a blending amount capable of exhibiting the effects of the present invention, but is usually 0 with respect to the osteoporosis prevention and / or amelioration agent as a whole. 0.0001 mass% or more, preferably 0.001 mass% or more, more preferably 0.01 mass% or more, still more preferably 0.1 mass% or more, and particularly preferably 1 mass% or more. The upper limit of the amount is preferably 35% by mass or less, more preferably 25% by mass or less, still more preferably 20% by mass or less, and particularly preferably 15% by mass or less with respect to the osteoporosis prevention and / or alleviating agent as a whole. .

  The dosage of the osteoporosis prevention and / or ameliorating agent of the present invention is not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately changed depending on various factors such as the age and condition of the administered living body to which it is applied. . In order to obtain the desired osteoporosis prevention and / or improvement effect, the preferred dose of the osteoporosis prevention and / or improvement agent is preferably 0.001 g / day to 100 g / day as the amount of ascorbic acid derivative per adult. .

  The osteoporosis preventive and / or ameliorating agent of the present invention can be used as it is as a final product (for example, food and drink, pharmaceuticals, quasi drugs, etc.). Moreover, it can use as an additive for food-drinks, an additive for pharmaceuticals, and an additive for quasi drugs. Thereby, the osteoporosis prevention and / or improvement effect can be provided to food / beverage products, pharmaceuticals, and quasi drugs.

  The osteoporosis preventive and / or ameliorating agent of the present invention may have an ascorbic acid derivative as an active ingredient, and may have a component (pharmacologically acceptable base) other than the ascorbic acid derivative. As an example of other components, there may be mentioned components (for example, storage stabilizers) that mainly ensure stability in storage and distribution. In addition, one or two or more types of components (preferably about 1 to 3 types, more preferably 1 type) selected from various components constituting the target final product (for example, foods and drinks, pharmaceuticals, quasi drugs, etc.) Degree).

  Components other than the ascorbic acid derivative contained in the osteoporosis prevention and / or ameliorating agent of the present invention are not particularly limited as long as the object of the present invention is not impaired. For example, excipients, disintegrants, binders, lubricants, coating agents, colorants, color formers, flavoring agents, flavoring agents, antioxidants, preservatives, flavoring agents, sour agents, sweeteners, strengthening From various agents, vitamins, swelling agents, thickeners, surfactants, etc. that do not impair the properties required for the formulation (for example, stability of the formulation). One type or two or more types can be selected according to the dosage form of the external product, food and drink, and the like. In addition, the component other than the ascorbic acid derivative may be another component having an effect of preventing and / or improving osteoporosis.

  The dosage form of the osteoporosis preventing and / or improving agent of the present invention is not particularly limited. For example, oral administration (eg, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.) and the like can be mentioned. Among these, a less invasive dosage form is preferable, and oral administration is more preferable. More preferably, the agent for preventing and / or improving osteoporosis of the present invention is orally administered as a zero-drink product.

  The dosage form of the osteoporosis prevention and / or amelioration agent of the present invention can be appropriately determined depending on whether it is a food or drink, a pharmaceutical product, or a quasi-drug, and is not particularly limited. Examples of dosage forms for oral administration include liquid (liquid), syrup (syrup), tablets (tablets, tablets), capsules (capsules), powders (granules, fine granules), soft capsules (Soft capsule), syrup (syrup), solid, semi-liquid, cream, and paste.

  The administration time of the osteoporosis prevention and / or ameliorating agent of the present invention is not particularly limited. It may be administered before the onset of osteoporosis or may be administered after the onset of osteoporosis. When it is administered after the onset of osteoporosis, it is preferably administered at the initial stage of onset.

  The agent for preventing and / or improving osteoporosis of the present invention can prevent its onset before onset of osteoporosis. In addition, after the onset of osteoporosis, the symptoms can be improved (relieved). Therefore, it can be used as a food or drink or pharmaceutical for preventing and / or improving osteoporosis. Osteoporosis is roughly classified into primary osteoporosis and secondary osteoporosis depending on the cause, but in the present invention, regardless of the cause of osteoporosis, prevention and improvement effects can be exhibited for any type of osteoporosis. . Examples of primary osteoporosis include postmenopausal osteoporosis, senile osteoporosis, osteoporosis associated with pregnancy, and the like. Examples of secondary osteoporosis include osteoporosis against a background of diseases such as diabetes. Moreover, the osteoporosis prevention and / or amelioration agent of the present invention can also exhibit a fracture prevention effect. The cause, site, degree, etc. of the fracture are not particularly limited, but a fracture caused by osteoporosis is the main target.

  The osteoporosis preventing and / or improving agent of the present invention can also be used as a fracture preventing agent, a bone mass increasing agent, a bone density increasing agent, and a bone strength increasing agent.

  The agent for preventing and / or improving osteoporosis of the present invention can also be referred to as an agent for preventing and / or improving bone ratio reduction. In osteoporosis due to diabetes, aging, etc., both bone resorption and bone formation decrease, so the bone ratio (BV / TV) decreases, but ascorbic acid derivatives can remarkably suppress the decrease in bone ratio. .

  The subject of taking the osteoporosis prevention and / or ameliorating agent of the present invention is not particularly limited, but for example, a subject who has already developed osteoporosis, a subject who is at risk of osteoporosis and fractures (the elderly, smokers, pregnant women, Postmenopausal women, obese, diabetics, etc.). Moreover, even a subject who has no particular problem can be ingested on a daily basis for the purpose of preventing osteoporosis or fracture, increasing bone mass, increasing bone density, and increasing bone strength.

  The osteoporosis preventing and / or improving agent of the present invention can be used as various foods and drinks. For example, beverages (soft drinks, carbonated drinks, nutritional drinks, powdered drinks, fruit drinks, milk drinks, jelly drinks, etc.), confectionery (cookies, cakes, gums, candy, tablets, gummies, buns, sheep cakes, puddings, jelly, Ice cream, sherbet, etc.), processed fishery products (kamaboko, chikuwa, hanpen, etc.), processed livestock products (hamburg, ham, sausage, winner, cheese, butter, yogurt, fresh cream, margarine, fermented milk, etc.), soup (powder) And soup, liquid soup, etc., staple foods (rice, noodles (dried noodles, raw noodles), bread, cereals, etc.), seasonings (mayonnaise, shortening, dressing, sauce, sauce, soy sauce, etc.). Furthermore, the osteoporosis prevention and / or amelioration agent of the present invention is a health food, functional food, health supplement (supplement), nutritional supplement, specific health food, medical food, sick food, infant food, It can also be used as food and drink such as food for care and food for the elderly. Among these, it is preferable to use as a health supplement, and more preferable to use as a tablet-like health supplement.

Examples 1 and 2 and Comparative Examples 1 and 2
Type 2 diabetes model mice (KKAy mice (8 weeks old, male)) were divided into three test groups, and 1% (W / V) ascorbic acid phosphate Mg salt (APM) (Example 1) was added to each test group. ) (N = 8), 1% (W / V) ascorbic acid-2-O-α-glucoside (A2G) (Example 2) (n = 9), distilled water (DW) (Comparative Example 1) (n = 9) was administered. The administration method was free intake as drinking water. The administration period was 14 weeks (finished at the age of 22 weeks).

  Meanwhile, distilled water (DW) was administered to healthy mice (C57BL / 6 mice (8 weeks old, male)) (Comparative Example 2) (n = 9). The administration method and administration period were the same as those of type 2 diabetes model mice.

  APM used was a commercial product manufactured by Showa Denko KK. A2G used was a commercial product manufactured by Hayashibara Biochemical Laboratory.

[Evaluation of bone density increase]
After the administration period, a tomographic image of the cancellous bone between the lower first molar and the root of each mouse was taken by X-ray CT, and the volume of the void portion was measured (the void area on the continuous tomographic image was integrated). The average value of each test group was calculated from the measured values. FIG. 1 shows the results of the volume (unit: AU (arbitrary unit)) of the canopy bone voids of Example 1 (APM) and Comparative Example 1 (DW). The cross section of the cancellous bone of Example 1 (APM), Example 2 (A2G), and Comparative Example 1 (DW) is shown in FIG. A cross section of the cancellous bone of Comparative Example 2 (healthy mouse) is shown in FIG. In FIG. 2 and FIG. 3, the part to which the arrow is attached is the canopy bone gap.

  In the type 2 diabetes model mouse, cancellous bone voids are seen. However, the volume of cancellous bone voids of type 2 diabetes model mice administered with APM was smaller than the volume of canopy bone voids of type 2 diabetes model mice administered with distilled water (FIG. 1). In the type 2 diabetes model mouse administered with A2G, a reduction in the volume of the void portion of the cancellous bone was observed as compared with the healthy mouse, similarly to the type 2 diabetes model mouse administered with APM (FIGS. 2 and 3). ).

Moreover, the bone mineral density (BMD) of the tomographic image of the cancellous bone between the roots photographed similarly was calculated.
BMD was compared by CT value of bone part excluding voids (average value of mice in each test group). The BMDs of Example 1 (APM), Comparative Example 1 (DW) and Comparative Example 2 (healthy mouse) are shown in FIG.
BMD of cancellous bone decreased in type 2 diabetes model mice (Comparative Examples 1 and 2). However, the BMD of the type 2 diabetes model mouse administered with APM (Example 1) was higher than the BMD of the type 2 diabetes model mouse administered with distilled water (Comparative Example 1) (FIG. 4).

  These results show that ascorbic acid derivatives improve the bone formation / bone resorption balance of cancellous bone to the bone forming side, improve bone density (bone / void ratio), and further improve BMD of the formed bone This shows that the strength of the bone itself is also improved. The results also show that ascorbic acid derivatives have the potential to prevent osteoporosis and fractures, reduce these risks, and improve osteoporosis symptoms.

Example 3 and Comparative Examples 3 and 4
Type 2 diabetes model mice (KKAy mice (8 weeks old, male)) were divided into three test groups, and 1% (W / V) ascorbic acid phosphate ester Mg salt (APM) (Example 3) was added to each test group. ) (N = 8), distilled water (DW) (Comparative Example 3) (n = 9). The administration method was free intake as drinking water. The administration period was 14 weeks (finished at the age of 22 weeks).

  Meanwhile, distilled water (DW) was administered to healthy mice (C57BL / 6 mice (8 weeks old, male)) (Comparative Example 4) (n = 9). The administration method and administration period were the same as those of type 2 diabetes model mice.

  APM used was a commercial product manufactured by Showa Denko KK.

[BV / TV evaluation of KKAy test]
After the administration period, a tomographic image of the dentition direction passing through the middle of the lower first molar and third molar root of each mouse was taken by X-ray CT, and cortical bone in a rectangular measurement area set at the lower root and anterior incisor And the area of the void portion was measured. The average value of each test group was calculated from the measured values.

  Details are as follows. The image was opened with soft winroof, converted into a monochrome image, binarized (threshold: 66), and a bone portion was extracted. Subsequently, the measurement area was set and the shape was measured. The measurement area is rectangular, the right end is the left end of the mesial root of the first molar, the left end is the mesial end of the incisor section, the upper end is the lower end of the first molar distal root, and the lower end is the range that does not protrude the mandible Set. The area of the bone part in the measurement area (BV) / the area of the entire measurement area (TV) was measured.

  FIG. 5 shows the results of BV / TV (bone area / measurement area area × 100) of Example 3 (APM), Comparative Example 3 (DW), and Comparative Example 4 (healthy mouse). The molar cross-sections of Example 3 (APM), Comparative Example 3 (DW), and Comparative Example 4 (healthy mouse) are shown in FIGS. The inside of the rectangular frame of FIGS. 6-8 is a measurement object site | part.

  As is clear from FIG. 5, BV / TV decreased in type 2 diabetic mice (Comparative Example 3). On the other hand, administration of APM drinking water (KAP: Example 3) suppressed the decrease in BV / TV and was at the level of healthy mice (BL: Comparative Example 4).

  These results show that ascorbic acid derivatives improve the bone formation / bone resorption balance of cancellous bone to the bone forming side, improve bone density (bone / void ratio), and further improve BMD of the formed bone This shows that the strength of the bone itself is also improved. This result also shows that ascorbic acid derivatives have the potential to prevent osteoporosis and fractures, reduce these risks, improve the symptoms of osteoporosis, and prevent bone ratio loss and reduce these risks. Shows to reduce.

Claims (6)

  An agent for preventing and / or improving osteoporosis comprising an ascorbic acid derivative as an active ingredient.   The osteoporosis preventive and / or ameliorating agent according to claim 1, wherein the ascorbic acid derivative is ascorbic acid phosphate magnesium salt and / or ascorbic acid-2-glucoside.   The osteoporosis preventive and / or ameliorating agent according to claim 1 or 2, wherein the osteoporosis is osteoporosis due to diabetes.   A preventive and / or ameliorating agent for reducing bone ratio, comprising an ascorbic acid derivative as an active ingredient.   The preventive and / or ameliorating agent according to claim 4, wherein the ascorbic acid derivative is an ascorbic acid phosphate magnesium salt.   One or more kinds selected from the group consisting of the osteoporosis prevention and / or improvement agent according to any one of claims 1 to 3 and the bone ratio reduction prevention and / or improvement agent according to claim 4 or 5. Food / beverage products containing agents.