JP2000198736A - Antiosteoporotic agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antiosteoporotic agent easily and commonly usable and capable of manifesting mild therapeutic and preventing effects by including a trehalose as an active ingredient. SOLUTION: This antiosteoporotic agent preferably as a preventing agent for osteoporosis, a therapeutic agent for the osteroporosis and a differentiation induction inhibitor of osteoclasts is obtained by including >=0.1% (wt./wt.) of a trehalose as an active ingredient and preferably another ingredient for facilitating the ingestion of the trehalose. In this case, a raw material and/or a material used for foods, e.g. water, an alcohol, a starch, a protein or a fiber may be formulated as the ingredient for facilitating the ingestion of the trehalose. Furthermore, a healthy food material such as a glucide for proliferating bifidus bacteria or a milk powder can be formulated. The trehalose is daily ingested so as to provide preferably 1-50 g/adult/day intake or ingested 1-5 times/week.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an anti-osteoporosis agent, and more particularly to an anti-osteoporosis agent containing trehalose as an active ingredient.

[0002]

2. Description of the Related Art Osteoporosis is also referred to as osteoporosis, and refers to a state in which bone has a qualitative change and its absolute amount decreases. In a living body, bone formation by osteoblasts and bone resorption by osteoclasts continue without interruption. If for some reason there is a difference between the rate of bone formation and the rate of bone resorption, and bone formation leans to a negative equilibrium, osteoporosis will develop. The onset factors of osteoporosis are roughly classified into environmental factors and genetic factors.In addition to aging, environmental factors include, for example, endocrine diseases such as hyperthyroidism, hypogonadism, Cushing's syndrome, and genetic factors. It has been pointed out that abnormal estrogen receptor genes, osteogenesis imperfecta, homocystinuria and the like have been reported. When osteoporosis develops, the width of cortical bone decreases,
As the medullary cavity expands, the trabecular bone of the cancellous bone decreases and becomes coarse. As osteoporosis progresses, the mechanical strength of the bones decreases, causing frequent complaints of back pain and joint pain,
Even a slight impact makes it easier to fracture.

[0003] In the treatment of osteoporosis, an analgesic is usually used first to relieve pain, and then an active vitamin D agent, a calcitonin preparation, an estrogen preparation, an anabolic hormone preparation, etc., which are involved in calcium metabolism, are administered. . As described above, most of the conventional osteoporosis treatment agents are hormone preparations. Since hormonal preparations can cause side effects, their use must be prescribed by a physician, and thus cannot be routinely used as a preventive agent by healthy subjects. The incidence of osteoporosis increases rapidly with age. With the advent of a full-fledged aging society, the development of anti-osteoporosis drugs that can be easily used regularly at home and exhibit mild therapeutic and preventive effects is also needed for a healthy and comfortable retirement. Have been.

[0004]

SUMMARY OF THE INVENTION In view of such circumstances, an object of the present invention is to provide an anti-osteoporosis which can be easily used regularly and exerts a mild therapeutic / preventive effect.

[0005]

Means for Solving the Problems When the present inventor searched various substances, trehalose, one of disaccharides,
When taken by mammals including humans, it has completely unexpectedly found that bone formation with a negative balance is adjusted to a normal state as expected and exerts a mild therapeutic / preventive effect on osteoporosis. That is, the present invention solves the above-mentioned problems by providing an anti-osteoporosis agent comprising trehalose as an active ingredient.

Trehalose is a disaccharide in which two molecules of glucose are bonded to each other via a reducing group, and is widely distributed in nature in bacteria, fungi, algae, insects, crustaceans and the like. In the fields of food, cosmetics and pharmaceuticals, the demand for trehalose as a sugar instead of sucrose is growing rapidly, but except for energy replenishment, moisturizing skin and regulating fatty acids in blood, In fact, the physiological effects of trehalose are hardly elucidated.

[0007] Trehalose is a known substance. However, as described above, the present invention is based on the unique finding that trehalose exerts a remarkable anti-osteoporosis effect in mammals, and the use of trehalose as an anti-osteoporosis agent is spearheaded by this invention. is there.

[0008]

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an anti-osteoporosis agent comprising trehalose as an active ingredient. As is well known, trehalose has three kinds of isomers called α, α isomers, α, β isomers, and β, β isomers having different binding modes. Since they exert similar anti-osteoporosis effects in mammals including humans, any of them can be advantageously used in the present invention. Therefore, the preparation method, purity and properties of the anti-osteoporosis agent of the present invention are not limited as long as one or more of these isomers are contained in an effective amount as a whole.

[0009] Trehalose can be prepared in various ways. This invention does not relate to the preparation of trehalose, so a detailed description is omitted.
JP-A-143876, JP-A-7-213283, JP-A-7-322883, JP-A-7-298
880, JP-A-8-66187, JP-A-8-66187
-66188, JP-A-8-336388 and JP-A-8-84586, in which a non-reducing saccharide-forming enzyme and a trehalose-releasing enzyme are allowed to act on a starch partial hydrolyzate. It is. According to this method, α, α-form of trehalose can be obtained in high yield from starch, which is an inexpensive material. Incidentally, commercially available products prepared by such a method include crystalline trehalose powder (trade name “trehaose”, a trehalose content of 98% or more per solid weight, sold by Hayashibara Shoji Co., Ltd.) and a trehalose-containing syrup (trade name “Trehaose”). Trehastar ", a trehalose content of 28% or more per solid weight, sold by Hayashibara Corporation. Note that α, α-forms can be added to maltose by, for example, Japanese Patent Application Laid-Open Nos. 7-170977 and 8-2633 by the same applicant.
It can also be obtained by allowing maltose / trehalose converting enzyme described in any of JP-A-8-149980 to act, or by combining known maltose phosphorylase and trehalose phosphorylase.

[0010] To prepare the α, β form of trehalose,
For example, Japanese Patent Application Laid-Open No. 4-144694 by the same applicant.
According to the method described in Japanese Patent Application Laid-Open No. HEI 4-179490, a mixture of partially hydrolyzed starch and lactose may be reacted with cyclomaltodextrin-glucanotransferase and β-galactosidase in this order. Further, β- and β-forms can be obtained by known chemical synthesis. In the present invention, trehalose does not necessarily have to be highly purified, and may be in the form of an unseparated composition with other carbohydrates specific to the preparation method, or in a mammal including human, trehalose may have anti-osteoporosis. It may be in the form of a mixture with other appropriate components which do not substantially hinder the action.

Trehalose, when ingested by mammals including humans, exerts an effect of adjusting the balance between bone formation and bone resorption to a normal state where it should be. That is, when balance is normal, it acts to maintain its normal state, and, for example, low-rotation osteoporosis in which bone formation falls below a normal level and bone mass decreases, such as senile osteoporosis. As in high-rotation osteoporosis, where bone resorption exceeds normal levels and bone loss decreases, such as hyperparathyroidism, there is a difference between the rate of bone formation and the rate of bone resorption, resulting in a balance of bone formation. When is tilted negatively, it acts to return its equilibrium to the normal state it should be. Due to these effects, when trehalose is taken by mammals including humans, if the bones are healthy, the healthy state is maintained and promoted, and if osteoporosis is present, low back pain associated with osteoporosis is maintained. In addition to reducing joint pain, it acts to increase bone mass and make it difficult to fracture. Therefore, the anti-osteoporosis agent referred to in the present invention includes all foods and pharmaceuticals, including beverages, containing trehalose as an active ingredient and taken for the purpose of treating and / or preventing osteoporosis. The unique effect of the anti-osteoporosis agent of the present invention can also be confirmed by, for example, a test described below using the weight of the femur in an ovarectomized mouse as an index.

The anti-osteoporotic agent of the present invention may be in the form of trehalose alone or in the form of a composition of trehalose and other components that facilitate the intake of trehalose. Compositions that facilitate the ingestion of trehalose are usually in the form of food or medicine, including forms as a tube-fed liquid meal and tube-fed infusion, more specifically, solution, suspension, emulsion, cream It is provided in the form of a solid food or pharmaceutical which is shaped into a shape, a paste, a powder, a granule, or any other desired shape. That is, in the form of food, for example, water, alcohol,
Ingredients ordinarily used in foods such as starches, proteins, fibers, sugars, lipids, vitamins, minerals, flavors, colorants, sweeteners, seasonings, spices, stabilizers, antioxidants, preservatives and / or The composition may be obtained by blending the ingredients as components that facilitate the ingestion of trehalose. Such a composition further comprises a Bifidobacterium-grown saccharide, powdered milk,
One or more health food materials such as milk protein hydrolyzate (casein calcium peptide, casein phosphopeptide), lactoferrin, soy isoflavone, blood meal, bone meal, shell powder, and coral powder can also be appropriately blended. Such foods may be in the form of a tube food or a tube infusion. In the case of a pharmaceutical form, for example, one or more of a carrier, an excipient, a diluent, and a stabilizer are blended as a component that facilitates ingestion of trehalose, and further, if necessary, treatment of osteoporosis. Usually used in, for example, calcium lactate, calcium glycerophosphate, calcium hydrogen phosphate and calcium L-aspartate, and further, an analgesic, anti-inflammatory, active vitamin D, vitamin K, calcitonin preparation, One of other drugs such as estrogen preparation and anabolic hormone preparation
Alternatively, a composition may be obtained by blending a plurality of components. Depending on the form of use, the anti-osteoporosis agent of the present invention usually contains trehalose in an amount of 0.1% (w / w) or more, preferably 1% (w / w).
w) or more.

The method of using the anti-osteoporosis agent of the present invention will be described by taking the case of humans as an example. The anti-osteoporosis agent of the present invention has a mild anti-osteoporosis action whether used orally or parenterally. Demonstrate. In addition, the anti-osteoporosis agent prevents the bone-related diseases or damages such as fractures and cracks in the bones in both oral and parenteral use, due to the above-mentioned effects, and prevents such diseases or damages. It is effective in improving and improving the therapeutic effect of the usual method of injury. Although it depends on the purpose of use, for example, when the purpose is to maintain or promote bone health or to prevent osteoporosis, it is usually taken orally in the form of food. For the purpose of treating osteoporosis, relieving low back pain and joint pain associated with osteoporosis, and improving the therapeutic effect of bone damage and disease, usually, food or liquid,
They are taken orally in the form of pharmaceuticals such as syrups, powders, granules, tablets and capsules, or, in some cases, parenterally in the form of injections, external preparations and the like. The dose is usually about 0.5 g to 100 g / adult / day, preferably about 1 g to 50 g / trehalose.
Adults / day, take daily, or
Ingest 1 to 5 times / week.

Next, the efficacy and safety of the anti-osteoporosis agent of the present invention will be described based on experimental examples.

[0015]

[Experiment 1] <Animal experiment> 4-week-old female ddY mice (34 / day) grouped based on body weight according to a conventional method
Group) was anesthetized with Nembutal and the ovaries were removed. From the next day, 0.01 g / kg body weight / time of crystalline trehalose powder (trade name “Trehaose”, trehalose content of 98% or more per solid weight, sold by Hayashibara Shoji Co., Ltd.) dissolved in an appropriate amount of distilled water was added. They were orally ingested once daily at a dose of 1 g / kg body weight / time or 1 g / kg body weight / time five times a week. Four weeks later, each individual was weighed, sacrificed according to a conventional method, the right and left femurs were excised, heated at 110 ° C. overnight, dried, and weighed. The feed used was breeding with a low calcium content, in which a difference in bone mass is likely to appear.

At the same time, a group in which the same amount of distilled water is orally ingested instead of the trehalose aqueous solution (Control 1), and estradiol which is a therapeutic agent for osteoporosis is replaced with the same amount of distilled water in place of orally ingesting the trehalose aqueous solution. 1mg dissolved
/ Kg body weight / time, intraperitoneal administration twice a week (Control 2), and mice undergoing laparotomy but not removing ovaries (sham operation), distilling the same volume in place of trehalose aqueous solution A group for ingesting water (control 3) was provided, and these were treated in the same manner as in the group for ingesting trehalose orally (trehalose-administered group) to serve as controls. Table 1 summarizes the dry weight of the femur in the trehalose-administered group and the controls 1 to 3. In addition, the tibia was excised from some of the individuals in the trehalose-administered group (trehalose dose: 0.1 g / kg body weight / time) and the trehalose-unadministered group (control 1 and control 3) according to a conventional method, and observed under a microscope. Specimens for microscopic observation were prepared by fixing the extracted tibia with a formalin solution according to a standard method, washing with water, decalcifying, cutting along the long axis, and treating with protease K to remove bone marrow cells. Prepared. The tibial specimen was observed with a low-vacuum scanning electron microscope (magnification: 24 ×), and the observed image was photographed. The results are shown in FIGS. FIG.
In the images shown in FIGS. 3 to 3, the white portion is the trabecular bone. Incidentally, osteoporosis occurring in mice from which ovaries have been removed is called ovariectomized osteoporosis, and is known to be an excellent model of postmenopausal osteoporosis, a type of senile osteoporosis.

[0017]

[Table 1]

The results in Table 1 indicate that trehalose, when taken orally by mammals, is not as fast-acting as estradiol, but significantly inhibits bone loss associated with osteoporosis. The suppression of bone loss was apparent when trehalose was ingested at a dose of about 0.1 g / kg body weight / time, and became even more remarkable at a dose of 1 g / kg body weight / time. This effect of trehalose can also be seen from the photographs of FIGS. That is, when the tibia shown in FIG. 3 is regarded as normal and FIG. 1 and FIG. 2 are compared with each other, as shown in the control 1, the sponge which is a typical finding of osteoporosis is seen in the lower part from the center of FIG. The trabecular bone loss and bone marrow cavity enlargement in the bone became remarkable, and it was mechanically weak,
In the trehalose-administered group, as shown in FIG. 1, the reduction of trabecular bone and the expansion of the medullary cavity were clearly suppressed, and were mechanically strong. When the mice were carefully observed over the entire test period, there was no abnormality due to the administration of trehalose. Although data are not shown, a system using sucrose instead of trehalose was established and tested in the same manner as in trehalose, and a significant difference was observed compared to the control in which distilled water was given to ovarectomized mice. Did not.

Next, from the group to which trehalose was administered at a dose of 0.1 g / kg body weight / time and the control 1 and control 3 groups, Similarly, the tibia was removed. Bone marrow cells were collected from each tibia in a conventional manner, and
% (V / v) α- supplemented with fetal bovine serum
In the MEM medium, a cell density of 1.5 × 10 ⁶ cells /
ml. Each bone marrow cell suspension was added to a 24-well plate at 0.5 ml / well. In each of these wells, according to a conventional method,
After treating the skull of a newborn ddY mouse with collagenase and dispase, 0.25 ml / well of a suspension of osteoblast-like cells having a cell density of 4 × 10 ⁴ cells / ml was suspended in a fresh medium having the same composition as described above. Was added. Further, in each well, was dissolved in a medium of the same composition as above,
A solution of 1α, 25-dihydroxyvitamin D _{3 at a} concentration of 4 × 10 ⁻⁹ M was added in an amount of 0.25 ml / well. The mixture of the cell suspension thus obtained was incubated at 37 ° C. in a 5% CO ₂ incubator with 1 × 10 ⁻⁹ M1α, 25-dihydroxyvitamin D ₃ and 10% (v / v) fetal calf serum. The cells were cultured for 6 days while appropriately replacing the containing α-MEM medium.

After culturing, the culture supernatant was removed, and the cells in the wells were fixed using formalin.
Cells showing tartaric acid-resistant acid phosphatase activity were stained according to a conventional method using "S-MS phosphate" and "Red Violet LB Salt" (both manufactured by Sigma). Incidentally, differentiated osteoclasts have the characteristic of exhibiting tartrate-resistant acid phosphatase activity and being multinucleated. After staining, each well was observed with an optical microscope, and the number of cells stained and showing multinucleation was counted for each well to obtain the number of osteoclasts. As a result, the number of osteoclasts in the well of control 1 was at least three times that of control 3, whereas the number of osteoclasts in the trehalose-administered group was about twice that of control 3, This indicates that trehalose has an action of suppressing the induction of osteoclast differentiation. There is a good correlation between the decrease in bone mass associated with osteoporosis and the induction of osteoclast differentiation (control 1) in the animal experiments described above. A good correlation was found between the inhibition of osteocyte differentiation induction (trehalose administration group). Therefore, the results shown in Experiment 1 above indicate that trehalose exerts a mild anti-osteoporosis effect by regulating the negatively-balanced osteogenesis to its normal state, and such an effect is attributed to trehalose. This suggests that the effect of inhibiting osteoclast differentiation induction is involved.

[0021]

[Experiment 2] <Clinical test> Thirty-four subjects (17 men and women) aged 60 to 72 years old complaining of back pain and joint pain associated with senile osteoporosis and post-traumatic osteoporosis.
After grouping into two groups so that the number of males and females was substantially the same, the test sample in Example 5 described below was used as a test sample except that the anti-osteoporotic agent of the present invention prepared by the method of Example 5 described below or trehalose was replaced with sucrose. One of the placebos prepared in the same manner as described above was ingested at a dose of 5 tablets / dose for one month after each meal. The test was contacted by a lab technician, who was interviewed periodically during the test for progress. After the end of the test, based on the results of the interview, the effect of the test sample was evaluated as “good,” “slightly effective,” “unchanged,” and “exacerbated,” using the index of alleviation of low back pain and / or joint pain associated with osteoporosis. The response rate (%) was defined as the percentage of the total number of subjects who answered "good" or "slightly effective" to the total number of subjects in each group.
Table 2 shows the results.

[0022]

[Table 2]

The results in Table 2 show that the anti-osteoporotic agent of the present invention is effective for alleviating low back pain and joint pain associated with osteoporosis. That is, the response rate of the group that took the placebo was 1
While the response rate was less than 0%, the response rate of the group that took the anti-osteoporosis agent of the present invention reached just over 40%. Moreover,
None of the subjects complained of physical and mental upset due to ingestion of the anti-osteoporosis drug of the present invention.
She answered that she had a feeling of relaxation and regular convenience, and that she had less trouble working and walking. These results
This indicates that the anti-osteoporosis agent of the present invention exerts a mild anti-osteoporosis effect.

[0024]

[Experiment 3] <Acute toxicity test> Crystalline trehalose powder (trade name “Trehaose”, trehalose content 98% or more per solid weight, in a physiological saline solution containing 5% (w / w) gum arabic), Hayashibara Corporation After dissolving an appropriate amount of (sales), the solution was sterilized according to a conventional method. Weight 20 to 2
After 5 g of ddY mice (10 / group) were injected intraperitoneally or orally by gastric tube, the progress was observed for 7 days. As a result, the maximum trehalose dose attempted, 15 g /
No deaths were observed at kg body weight. This result indicates that the anti-osteoporosis agent of the present invention is commonly used and safe in mammals including humans.

Hereinafter, embodiments of the present invention will be specifically described based on examples.

[0026]

Example 1 <Health food> According to a conventional method, a temperature of 20
The potatoes which had been self-digested with reducing sugars by storing at 85 ° C and a humidity of 85% for 2 weeks were washed with water, peeled and sorted,
The slices were 1.5 mm thick using a centrifugal slicer. After the starch on the slice surface was removed by washing with water, the slice was drained, oiled at a temperature of 170 ° C. for about 5 minutes, and drained.
Then, using a salter, 7 parts by weight of salt, 3 parts by weight of crystalline trehalose powder (trade name “Trehaose”, trehalose content of 98% or more per solid weight, sold by Hayashibara Shoji Co., Ltd.) and an appropriate amount of spices The resulting powdered seasoning was evenly sprinkled and then transferred to a weighing and filling machine where it was weighed, filled and packaged to obtain a trehalose-containing snack.

The product having good taste and flavor is useful as a health food for maintaining and promoting bone health.

[0028]

Example 2 <Health food> A crystalline trehalose powder (trade name “Trehaose”, 25 parts by weight of well-kneaded butter)
18 parts by weight of a trehalose content per solid weight of 98% or more (manufactured by Hayashibara Shoji Co., Ltd.) and 10 parts by weight of a chicken egg were added in this order, and the mixture was stirred to form a cream. 47 parts by weight of flour are added to the mixture, kneaded, wrapped in a cloth and left for 20 minutes, and the obtained dough is formed into a rod having a diameter of 3 cm.
Wrapped in paraffin paper and left at 4 ° C. for 2 hours. Then, the dough was sliced into a thickness of 5 mm, arranged on an oiled top plate, baked in an oven at 170 ° C. for 10 minutes, and trehalose-containing syrup (trade name “Trehastar”,
A trehalose content of 28% or more per solid weight, sold by Hayashibara Shoji Co., Ltd.) was applied and baked at the same temperature for another 10 minutes to obtain an ice box cookie containing trehalose.

The product having good taste and flavor is useful as a health food for maintaining and improving bone health.

[0030]

Example 3 <Health food> 7 parts by weight of freeze-dried black tea extract powder and trehalose-containing syrup (trade name “Trehastar”, trehalose content of 28% or more per solid weight,
Hayashibara Shoji Co., Ltd.) 3 parts by weight dissolved in an appropriate amount of water,
The obtained solution was sprinkled on 90 parts by weight of black tea leaves that had been fermented and dried according to a conventional method. The black tea leaves were sieved, cut, finished and dried by a conventional method to remove foreign substances using a sorter, and then packed in tea bags of 2 g each using Japanese paper to obtain tea bags containing trehalose.

The product is leached in 180 ml of cold water for about 10 minutes, or 180 m of hot water at 90 to 100 ° C.
1 to drink for about 2 minutes. This product, which has good taste and flavor, is useful as a health food that maintains and promotes bone health.

[0032]

Example 4 <Health food> Maltotetraose-containing syrup (trade name "TETRAP", content of maltotetraose per solid weight of 50% or more, sold by Hayashibara Shoji Co., Ltd.)
2.7 parts by weight, trehalose-containing syrup (trade name “Trehastar”, trehalose content 28% or more per solid weight, sold by Hayashibara Corporation) 7 parts by weight, coffee extract 5 parts by weight, whole milk powder 2.2 Parts by weight, 1 part by weight of skim milk powder, 0.04 parts by weight of sucrose fatty acid ester, 0.06 parts by weight of an overlay and 82 parts by weight of water were blended according to a conventional method to obtain a trehalose-containing coffee beverage.

This product having good taste and flavor is useful as a health food for maintaining and improving bone health.

[0034]

Example 5 <Health Supplement> 55 parts by weight of crystalline trehalose powder (trade name "Trehaose", trehalose content of 98% or more per solid weight, sold by Hayashibara Shoji Co., Ltd.), 40.5 parts by weight of corn starch, and crystals 2.5 parts by weight of cellulose were mixed and kneaded while spraying and dropping an appropriate amount of water according to a conventional method, followed by granulation in a fluidized bed, followed by pulverization and sizing to obtain a powder for tableting. After uniformly mixing 2 parts by weight of a sucrose fatty acid ester as a lubricant,
Tableting was performed with a tableting machine equipped with a 1 mm punch to obtain tablets containing trehalose (about 300 mg / tablet).

This product, which is easy to ingest and has excellent disintegration properties in the digestive tract, is useful as a health supplement for maintaining and improving bone health.

[0036]

Example 6 <Health supplement> Crystalline trehalose powder (trade name “Trehaose”, trehalose content of 98% or more per solid weight, sold by Hayashibara Corporation) 39
Parts by weight, natural coral powder 25 parts by weight, beef bone powder 9 parts by weight,
Powdered yogurt 12 parts by weight, guar gum 10 parts by weight,
1.9 parts by weight of vitamin C and glycosylated vitamin P
One part by weight was kneaded while spraying and dropping an appropriate amount of water according to a conventional method, granulated in a fluidized bed, pulverized, and sized to obtain a powder for tableting. Sucrose fatty acid ester as a lubricant
After uniformly mixing 3 parts by weight, the mixture was tableted with a tableting machine equipped with a punch having a diameter of 6 mm to obtain tablets containing trehalose (about 200 mg / tablet).

This product is useful as a health supplement that maintains and promotes bone health because calcium is reinforced and easy to ingest.

[0038]

As described above, the present invention exerts a mild anti-osteoporosis effect in mammals including humans by regulating trehalose to negatively-balanced bone formation to a normal state. It is based on the knowledge that. Because of this action, the anti-osteoporosis agent of the present invention containing trehalose as an active ingredient, when taken by a healthy person, maintains and promotes bone health and prevents osteoporosis. In addition, patients suffering from senile osteoporosis including postmenopausal osteoporosis, associated with osteoporosis, for example, hyperthyroidism, hypogonadism, Cushing's syndrome, osteogenesis imperfecta, patients suffering from homocystinuria, trauma and steroids When taken by patients whose bones have become fragile due to side effects associated with excessive administration of hormones, as well as patients with abnormal estrogen receptor genes, they can reduce back pain and joint pain associated with osteoporosis, increase bone mass, and increase bone fractures. Make it difficult to do. The anti-osteoporosis agent of the present invention further has an effect of enhancing the therapeutic effect of a bone-related disease or injury such as a fracture or a bone crack by an ordinary method. In addition, since trehalose is a carbohydrate that is widely distributed in nature, it can be safely used without worrying about side effects.

[Brief description of the drawings]

FIG. 1 is a photograph (24 × magnification) of a tibia of a mouse in a trehalose administration group, taken under a low vacuum scanning electron microscope.
5 is a halftone image displayed on the display of FIG.

FIG. 2 is a halftone image displayed on a display of a photograph (24 × magnification) of a tibia taken with a low vacuum scanning electron microscope of an ovariectomized mouse in a trehalose non-administration group.

FIG. 3 is a halftone image displayed on a display of a photograph (24 × magnification) of a tibia taken with a low-vacuum scanning electron microscope of a non-ovariectomized mouse in a trehalose non-administration group.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat ゛ (Reference) A61P 43/00 A61K 31/00 643D (31) Priority claim number Japanese Patent Application No. 10-316706 (32) Priority date November 6, 1998 (11.6 November 1998) (33) Countries claiming priority Japan (JP) F-term (reference) 4B018 LB01 LB08 LE03 MD29 ME05 4B032 DB40 DG20 DK12 DL20 4C086 AA01 AA02 EA01 MA01 MA02 MA04 MA52 NA14 ZA97 ZB21

Claims (6)

[Claims] 1. An anti-osteoporotic agent comprising trehalose as an active ingredient. 2. The anti-osteoporotic agent according to claim 1, comprising trehalose as an active ingredient and other components that facilitate the intake of trehalose. 3. The anti-osteoporosis agent according to claim 1, which comprises trehalose in an amount of 0.1% (w / w) or more. 4. The anti-osteoporosis agent according to claim 1, 2 or 3 as an osteoporosis prevention agent or an osteoporosis treatment agent. 5. The anti-osteoporotic agent according to claim 1, 2, 3, or 4 in the form of a food. 6. The anti-osteoporosis agent according to claim 1, which is used as an osteoclast differentiation induction inhibitor.