WO2007132714A1

WO2007132714A1 - Agent for increasing bone density

Info

Publication number: WO2007132714A1
Application number: PCT/JP2007/059620
Authority: WO
Inventors: Katsuhiko Ooyama; Jian Wu; Michio Kasai; Keiichi Kojima
Original assignee: The Nisshin Oillio Group, Ltd.
Priority date: 2006-05-16
Filing date: 2007-05-09
Publication date: 2007-11-22
Also published as: JPWO2007132714A1; TW200812569A

Abstract

It is intended to provide an agent for increasing bone density which can increase bone density and thus exerts preventive and therapeutic effects on diseases relating to bone such as osteoporosis, osteoporosis caused by menopause or hyperparathyroidism, secondary osteoporosis or retarded osteogenesis caused by gonadal dysfunction, more specifically speaking, an agent for increasing bone density which comprises as the active ingredient a medium chain fatty acid and/or an acyl glycerol containing a medium chain fatty acid. It is also intended to provide a food, a drink, a drug or the like which has an effect of increasing bone density and is useful in preventing and treating osteoporosis, bone fracture and so on. An agent for increasing bone density which comprises as the active ingredient a medium chain fatty acid and/or an acyl glycerol containing a medium chain fatty acid. A food or a drink which contains this agent for increasing bone density and is useful in preventing or treating osteoporosis.

Description

Specification

Bone density increasing agent

Technical field

[0001] The present invention relates to foods and pharmaceutical compositions useful for the prevention and treatment of diseases associated with bone loss such as osteoporosis. More specifically, the present invention relates to a medium-chain fatty acid and / or medium-chain fatty acid, which can obtain effects such as an increase in bone density by ingesting the power of ingestion as it is or added to foods and pharmaceuticals. The present invention relates to a bone density increasing agent containing acylglycerol, foods and drinks containing the same, and use in medicines.

Background art

[0002] In recent years, the life expectancy has continued to grow due to advances in medicine, etc. In the aging society that accompanies this, how to enrich the old age (quality of life) This is a very important issue. For this, it is important that the mind and body are healthy, and how to slow the progress of aging is the biggest problem. From this point of view, various aging phenomena have been discussed, and osteoporosis as a typical senile disease has been regarded as a problem. Osteoporosis is a systemic disease that makes bones brittle and prone to fractures. In addition to being painful by causing femoral neck fractures and compression fractures of the spine, falling into a bedridden state is not only a medical problem but also a social problem.

[0003] Under normal conditions, adult bones constantly undergo remodeling and maintain a balance of bone metabolism. In other words, in order to mobilize calcium necessary for life activity from bone into the blood, osteoclasts break down and absorb calcified tissue (bone resorption), and collagen and calcium necessary for maintaining bone strength are boned. By maintaining a good balance with the system in which blasts and bone cells are deposited on the bone as the bone matrix (bone formation), the bones will not fluctuate. Reborn. However, such abnormalities in bone metabolism occur, that is, bone resorption exceeds bone formation, and bone mass, that is, bone density, decreases, resulting in bone weakening.

[0004] Reduced bone density is due to osteoporosis, menopause, or hyperparathyroidism caused by steroid administration. It is found in many bone-related diseases, such as osteoporosis, secondary osteoporosis, and delayed bone formation due to gonadal dysfunction, causing fractures, bone deformation, pain, and dysfunction of organs and parts other than bone There is. As the aging population increases, there is a need to develop effective drugs that can cope with such a decrease in bone density, particularly drugs that increase bone density. The cause of decreased bone density is known to be related to a decrease in female hormones such as estrogen. For this reason, estrogen replacement therapy is performed in which estrogen such as estradiol is supplemented to prevent a decrease in bone density (see, for example, Patent Document 1). However, this estrogen replacement therapy may have side effects such as uterine irregular bleeding and increase the risk of developing tumors such as cervical cancer or breast cancer. For this reason, attempts to use progesterone in combination with estrogen to reduce this side effect have not always produced satisfactory results (see, for example, Patent Document 2).

[0005] In addition, from the viewpoint of the initial increase in bone density and prevention of osteoporosis, it is recommended to take a sufficient amount of meal power, vitamin D, vitamin K, and the like. In order to take these nutrients efficiently, it is necessary to pay attention to the diet. At present, only those who have a sense of crisis are doing it. These nutrients are also supplied as health foods such as tablets and supplements, but at present the problems of absorption, stability and price have not been solved. Under such circumstances, it is desired to develop a safe material with good absorbability, which can be provided at low cost and has an effect of increasing bone density and preventing osteoporosis.

[0006] On the other hand, osteoporosis due to decreased bone density and a disease called PEM are closely related.

Protein 'energy malnutrition (Protein Energy Malnutrition; hereinafter abbreviated as “PE M”) is a serious clinical nutrition problem in various countries around the world (Non-patent Document 1). According to the 1990 WHO World Health Statistics, there are approximately 52 million people affected worldwide and 295,000 deaths per year. In Japan, 30 to 40% of nursing home residents nationwide suffer from PEM, which can be said to be the biggest nutrition problem for the elderly (Non-patent Document 2). People with serum albumin levels of 3.5 g / dl or less are diagnosed with PEM, and those who have a relative risk of death more than four times higher than non-PEM elderly after one year (Non-Patent Document 3) It is recognized as a serious disease.

[0007] In healthy adults, the difference between the amount of protein consumed and the amount of protein excreted outside the body, the so-called The nitrogen balance is approximately ± 0, so the body protein pool is always constant. However, in some elderly people, the amount of ingested protein is less than the amount of excreted protein due to a number of factors such as decreased appetite, unfavorable taste, and decreased digestive absorption capacity associated with aging, resulting in a negative nitrogen balance. . In these individuals, the body protein pool tends to decrease over time, and the effects of this decrease include weight loss, muscle and visceral protein content, bone formation inhibition (Non-Patent Document 4), and serum albumin levels. As it manifests.

[0008] Many elderly people suffer from fractures due to osteoporosis and become bedridden due to it. On the other hand, when bedridden for several years, bone becomes fragile and osteoporosis progresses. Therefore, osteoporosis and a bedridden state are both a cause and a result (Non-patent Document 5). Also, bedridden elderly people often have serum hypoalbuminemia, a typical symptom of PEM (Non-patent Document 6). Therefore, osteoporosis and PEM are considered to be important in preventing PEM, which worsens life prognosis, by reducing the risk of osteoporosis by increasing bone density, which is deeply related to osteoporosis.

[0009] In the treatment of osteoporosis, in addition to the above-described method of supplementing estrogen, for example, ipriflavone, activated vitamin D3, bisphosphonate, vitamin K2, calcitonin and the like have been developed. However, since calcitonin is a peptide, it can only be administered by injection.Ibriflavone administration induces gastrointestinal damage.Excessive activation of vitamin D3 induces hypercalcemia and causes urinary calculi and digestive disorders. cause, the administration of bisphosphonates would also inhibit bone formation, vitamin Κ2 have limited patients administered also have a blood coagulation, there ^s problems and side effects force the like, respectively.

[0010] Thus, for example, as disclosed in Patent Document 3, mixing of medium-chain glycerides with the above bisphosphonate to suppress inhibition of bone formation of bisphosphonate has also been studied. .

Patent Document 1: Japanese Patent Laid-Open No. 145024

Patent Document 2: JP-A-7-267858

Patent Document 3: Special Table 2001—519398

Non-patent document 1: Current significance of protein's energy nutrition disorder, “clinical nutrition” , 1999, 94 卷, No. 3, 270 pages

Non-patent document 2: Nutrition management service for PEM improvement of the elderly, "Clinical nutrition", Medical and Dental Publishers, 1999, 94 卷, No. 4, p. 406

Non-Patent Document 3: Serum albumin level and physical disability as predictors of mortality in older persons. "JAMA", USA, American Medical Association, 1994, 272, 13, No. 1036

Non-Patent Document 4: The effects oi recombinant human parathyroid hormon e, rhPTH (l-84), on bone mass in undernourished rats, Journal of Endocrinology, USA, Society for Endocrinology, 2002, 174 卷, 419

Non-Patent Document 5: Complications of Bedridden Osteoporosis Patients, “Japanese Clinical”, Nippon Clinical Co., Ltd., 2004, 62 卷, Zhou Zhi IJ 2, 655

Non-patent document 6: Protein nutritional disorder in the elderly, “Clinical nutrition”, Bio-Dental Publishing Co., Ltd., 1999, 94 、, No. 4, p. 401

Disclosure of the invention

Problems to be solved by the invention

However, the medium chain glyceride used in Patent Document 3 is an absorption promoter for Ca and Mg, which gives a synergistic effect on the bone resorption inhibitory action of bisphosphonate. It is only used and medium chain glycerides themselves are not used to improve bone density.

[0012] Medium-chain fatty acids and / or acyl-glycerols containing medium-chain fatty acids are directly transported to the liver via the portal vein where digestion and absorption are fast and are quickly decomposed into energy. It is characterized by being difficult to accumulate in fat cells that are easily consumed. For this reason, it is known that medium chain fatty acids and / or acyloglycerides containing medium chain fatty acids are useful for body fat reducing agents and the like, but there has been no report on bone density.

[0013] The present invention improves the bone density, thereby to osteoporosis, osteoporosis due to menopause or hyperparathyroidism, secondary osteoporosis, bone formation delay due to gonadal dysfunction, etc. An object of the present invention is to provide a bone density increasing agent effective for the prevention and treatment of related diseases, specifically, a bone density increasing agent containing medium-chain fatty acid and / or acidoleglycerol containing medium-chain fatty acid as an active ingredient. And Furthermore, an object of the present invention is to provide foods and drinks, pharmaceuticals, etc. useful for the prevention and treatment of osteoporosis, fractures, etc., which have an effect of improving bone density.

Means for solving the problem

[0014] As a result of diligent research, the inventors of the present invention have found that medium chain fatty acids and / or a acylglycerol containing a medium chain fatty acid, preferably triacylglycerol whose constituent fatty acid consists only of a medium chain fatty acid (hereinafter referred to as "medium chain fatty acid" It was found that "fatty acid triglycerides" or "MCT") may improve bone density and thereby prevent osteoporosis.

[0015] Further, by using a bone density increasing agent containing medium-chain fatty acid and / or acidoleglycerol containing medium-chain fatty acid in general foods, health foods, and functional foods, bone density can be improved. I found out that I can plan.

Specifically, the present invention provides the following.

[0017] (1) Provided is a bone density increasing agent containing as an active ingredient an acyloleglycerol containing a medium chain fatty acid and / or a medium chain fatty acid.

[0018] According to this embodiment, a medium-chain fatty acid and a acylglyceose containing Z or medium-chain fatty acid, preferably a medium-chain fatty acid triglyceride, are administered to a rat in addition to a feed, as described later. Since the density is improved, it functions as a bone density increasing agent. This effect of increasing bone density is highly manifested in the distal femur, which is important for the prevention of osteoporosis (site that contains a lot of cancellous bone). It is also increased by combining exercise load

[0019] Osteoporosis and the like are diseases caused by bone resorption exceeding bone formation, bone mass, that is, bone density decreases and bone weakening occurs. By doing so, it is possible to prevent and improve bone-related diseases such as osteoporosis, secondary osteoporosis, and delayed bone formation due to gonadal dysfunction.

[0020] (2) The bone density increasing agent according to (1), wherein the medium chain fatty acid is a fatty acid having 6 to 12 carbon atoms. [0021] According to this aspect, the fatty acid residue of the acylglycerol containing medium-chain fatty acid and / or medium-chain fatty acid has 6 to 12 carbon atoms, so that it is easily absorbed in the body. For this reason, the bone density increasing effect is more effectively performed.

(3) The acyl glycerol containing the medium chain fatty acid is a medium chain fatty acid triglyceride (

A bone density increasing agent according to 1) or (2) is provided.

[0023] (4) Provided is a food or drink containing the bone density increasing agent according to any one of (1) to (3).

[0024] According to this aspect, since the food and drink contain the bone density increasing agent, the bone density can be improved by daily intake of this food and drink. Therefore, bone-related diseases such as osteoporosis, secondary osteoporosis, and delayed bone formation due to gonadal dysfunction can be prevented and improved.

[0025] In addition, the medium chain fatty acid and Z or medium acid glycerol containing medium chain fatty acid contained in the bone density increasing agent of the present invention is easily consumed as energy, so that it does not accumulate in fat cells without the force S. Even if it is taken on a daily basis, it is difficult to accumulate as body fat. Therefore, even if taken continuously on a daily basis, there is little risk of becoming a lifestyle-related disease such as diabetes caused by the accumulation of body fat.

[0026] (5) Provided is a food or drink according to (4), which is labeled for use in the prevention and improvement of osteoporosis.

[0027] (6) Provided is a food or drink described in (4) or (5), which is preferably used in combination with exercise, and is labeled as such.

[0028] (7) Provided is a method of using a medium chain fatty acid and / or a acylglycerol containing a medium chain fatty acid to produce a bone density increasing agent.

[0029] Medium chain fatty acid and Z or medium chain fatty acid acylglycerol has the effect of increasing bone density as described above, and thus is used as a raw material for producing a bone density increasing agent.

[0030] (8) Provided is an osteoporosis-preventing agent comprising a medium-chain fatty acid and Z or a acylglyceride containing a medium-chain fatty acid as effective components.

[0031] (9) Effective production of medium chain fatty acid and acyl glycerol containing Z or medium chain fatty acid The present invention provides a therapeutic agent for osteoporosis.

[0032] According to the embodiments of (8) and (9), the medium chain fatty acid and / or the acylglycerol containing the medium chain fatty acid has the effect of increasing the bone density as described above. The weakening of bones is prevented. Further, it is possible to increase the bone strength by increasing the decreased bone mass, that is, the bone density. For this reason, medium chain fatty acid and / or asinoleglycerol containing medium chain fatty acid is effective in preventing or treating osteoporosis.

[0033] (10) Provided is a method for using medium chain fatty acid and Z or medium chain fatty acid acylglycerol as any one of bone density increasing agent, osteoporosis preventive agent, and osteoporosis therapeutic agent.

[0034] Since medium chain fatty acid and Z or medium chain fatty acid acylglycerol has the effect of increasing bone density as described above, bones that have decreased due to inclusion in tablets, food and drink, etc. It can be used to increase the density or prevent the bone density from decreasing, and is used as a bone density increasing agent, osteoporosis preventing agent, or osteoporosis therapeutic agent.

The invention's effect

[0035] Since the bone density increasing agent of the present invention has a bone density increasing action, it is not only taken as an easily ingested granule, but also can be easily ingested as a food or drink that is eaten on a daily basis. It is useful for the prevention or treatment of various bone diseases such as fractures, rheumatism, arthritis, low back pain, and osteoporosis, and is particularly useful for the treatment or prevention of osteoporosis in the elderly. It is highly effective in the treatment of diseases caused by calcium deficiency and low bone mass.

[0036] Further, the active ingredient is a medium chain fatty acid and / or an acidoleglycerol containing a medium chain fatty acid, preferably a medium chain fatty acid triglyceride, which is easily absorbed into the body and is easily consumed as energy in the body. Since it is rarely accumulated in cells, it is difficult to accumulate as body fat even if it is taken on a daily basis.

[0037] For this reason, since there is less fear of becoming a lifestyle-related disease such as diabetes caused by the accumulation of body fat, etc., according to the present invention, an excellent bone density increasing effect can be received, and at the same time, absorption It is possible to provide a bone density increasing agent excellent in properties, safety and the like. BEST MODE FOR CARRYING OUT THE INVENTION

[0038] Hereinafter, embodiments of the bone density increasing agent of the present invention will be specifically described.

[0039] The present invention relates to a bone density increasing agent comprising a medium chain fatty acid and / or a acyl glycerol containing a medium chain fatty acid, preferably a medium chain fatty acid triglyceride as an active ingredient.

[0040] (Bone density increasing agent)

Examples of preferred medium chain fatty acids contained in the bone mineral density increasing agent of the present invention include fatty acids having 6 to 12 carbon atoms such as n-hexanoic acid (cabronic acid), n- Examples include octanoic acid (caprinoleic acid), n-decanoic acid (capric acid), and lauric acid, and one or more of these can be used. Among these, saturated fatty acids having 8 to 10 carbon atoms, particularly n-octanoic acid and n-decanoic acid are preferable.

[0041] The method for producing the medium chain fatty acid used in the present invention is not particularly limited. For example, palm kernel oil or coconut oil containing medium chain fatty acid is hydrolyzed and then refined to obtain strength. S can. Moreover, a commercial item and a reagent can also be used.

[0042] The acylglyceryl containing a medium chain fatty acid contained in the bone density increasing agent of the present invention is an ester of glycerin and a fatty acid, and at least one of the constituent fatty acids is an ester composed of a medium chain fatty acid. Depending on the degree of esterification, monoacyldaricerol, diacylglycerol, and triacylglycerol can have one or more of these.

[0043] In the case of diacylglycerol and triacylglycerol, all of the constituent fatty acids may be medium-chain fatty acids, or long-chain fatty acids may be contained in addition to the medium-chain fatty acids. Here, the long chain fatty acid means a fatty acid having 14 or more carbon atoms.

[0044] Considering availability, flavor, suitability for cooking, and exerting an effect with a small amount of use, triglyceryl glycerol is more preferable for acyl glycerol containing fatty acids and / or medium chain fatty acids. Among them, it is most preferable to use a medium chain fatty acid triglyceride in which all of the constituent fatty acids are medium chain fatty acids.

[0045] Medium chain triglycerides are generally referred to as MCT (Medium Chain Triglycerides), and the constituent fatty acids are triacylglycerols composed of fatty acids having 6 to 12 carbon atoms, preferably 8 to 10 carbon atoms. It is. Medium-chain fatty acid triglycerides contain one type of fatty acid. Even if it is a constituent fatty acid, it may be a constituent fatty acid containing two or more kinds of fatty acids.

[0046] When the constituent fatty acid is a medium-chain fatty acid triglyceride having one kind of fatty acid power, the fatty acid is preferably n-octanoic acid or n-decanoic acid.

[0047] In the case of a medium-chain fatty acid triglyceride composed of two types of fatty acids, the fatty acid is preferably n-octanoic acid and n-decanoic acid. Further, in that case, the mass ratio of n_octanoic acid and n_decanoic acid in all the constituent fatty acids is preferably a force S of 40Z60 to 90/10, more preferably a force of 60/40 to 85/15, Most preferred is 70 / 30-80 / 20.

[0048] As a method of measuring the mass ratio of octanoic acid and decanoic acid in all fatty acids of the acyl acylglycerol, for example, the fatty acid constituting the acyl acylglycerol is methyl esterified.

Quantitative analysis can be performed by gas chromatography.

[0049] As commercial products of medium chain fatty acid triglycerides, products manufactured by Nisshin Oilio Group Co., Ltd .: 0

DO (registered trademark).

[0050] The method for producing acylglycol containing medium chain fatty acid used in the present invention is not particularly limited.

[0051] For example, asinoleglycerol, whose constituent fatty acid consists only of medium-chain fatty acids, is obtained by esterifying the medium-chain fatty acids obtained by hydrolysis of palm kernel oil and palm oil, followed by purification. Thereafter, it can be obtained by purification treatment.

[0052] The medium-chain fatty acid and / or acyl-glycerol containing the medium-chain fatty acid contained in the bone density increasing agent of the present invention has a good solubility in fats and oils, and therefore is suitably combined with fats and oils. Thus, an oil and fat composition can be obtained.

[0053] The oil / fat composition or processed oil / fat product is very preferable in terms of absorbability because it is expected to be absorbed together with the oil. Further, by increasing the amount of medium-chain fatty acid and Z or medium chain fatty acid-containing acylglycerol, it is possible to enjoy an extremely excellent increase in bone density.

[0054] Further, the bone density increasing agent of the present invention has other physiological activities for the purpose of improving the function, in particular, synergistically improving the bone density increasing effect, assisting the bone density increasing effect, and improving the absorbability. It can be used in combination with components and the like.

[0055] In particular, when used for food and drink, feed, etc., it is preferable to combine with other physiologically active ingredients. Other physiologically active ingredients are not particularly limited as long as their physiological functions are clear, but for example, oily ingredients for improving the absorption in the body and increasing the efficiency of the effects, for nutritional enhancement Various vitamins, minerals, amino acids, and other physiologically active substances.

[0056] Oil components include soybean oil, rapeseed oil, oleic rapeseed oil, corn oil, sesame oil, sesame salad oil, perilla oil, linseed oil, peanut oil, safflower oil, safflower oil, safflower oil, sunflower oil, and high oleic acid Sunflower oil, cottonseed oil, grape seed oil, macadamia nut oil, hazelnut oil, cabotya seed oil, tarmi oil, coconut oil, tea seed oil, sesame oil, borage oil, olive oil, rice bran oil, wheat germ oil, beef fat, lard, chicken fat Fish oil, seal oil, algae oil, oils and fats that have been low-saturated due to quality improvement, hydrogenated oils and oils, fractionated oils and the like.

[0057] With regard to various vitamins, minerals, amino acids and the like for enhancing nutrition, it is desirable that there are no particular restrictions, but those specified in the Food Additives Official Document.

[0058] As other physiologically active substances, for example, lignan, coenzyme Q, phospholipid, oryzanol and the like can be blended.

[0059] The bone density increasing agent comprising the medium chain fatty acid and / or the acyl chain glycerol containing the medium chain fatty acid as an active ingredient has the above-described bone density increasing effect. That is, by directly or indirectly taking the bone density increasing agent of the present invention, the bone density increasing effect can be enjoyed. Furthermore, it is possible to obtain a more favorable effect by taking it continuously.

[0060] Here, the active ingredient means that it contains an amount that exhibits the effect of increasing bone density. Therefore, the content of the medium chain fatty acid and / or the acidoleglycerol containing the medium chain fatty acid in the bone density increasing agent of the present invention is not particularly limited as long as it is an amount that can exert the effect of increasing bone density. Depending on the intake and purpose of use, it may be adjusted as appropriate. However, if the effect is to be exerted with a small amount, it is preferable that the content is large. [0061] For example, the content of the medium chain fatty acid and / or the acino glycerol containing the medium chain fatty acid in the bone density increasing agent is preferably:! To 100% by mass, and is preferably 50 to 100% by mass. It is more preferred 70 ~: 100% by mass is particularly preferred 80 ~ 100% by mass, particularly preferred.

[0062] Further, in order to exert an effect with a small use amount, it is most preferable that the acylglycerone containing a medium chain fatty acid is a medium chain fatty acid triglyceride.

[0063] In addition, the above-described bone density increasing effect of the bone density increasing agent of the present invention can be obtained more remarkably when exercise is used in combination, as will be described in detail in Examples described later. There is an approximate correlation between the exercise load in rats and the exercise load in humans. In other words, the maximum exercise intensity of the running exercise in the growing rat is about 40 m / min, and it can be said that this exercise intensity corresponds to human aerobic exercise. Therefore, according to the rat test results, it is possible to increase the bone density of humans by using exercise that is 40 to 60% of the maximum oxygen intake of healthy humans.

[0064] Further, the amount of intake for obtaining a bone density increasing effect by taking the bone density increasing agent of the present invention varies depending on the form of intake, sex, body weight, physical condition, etc. of the subject and is particularly limited. However, for example, the intake amount as a medium chain fatty acid when a bone density increasing agent is ingested is most preferably 14 g / day or more.

[0065] The bone density increasing agent of the present invention is characterized by containing a medium chain fatty acid and / or a acyl glycerol containing a medium chain fatty acid, and includes a wide variety of foods and drinks such as fluid foods, health foods, infant foods, etc. Can be used in the field.

[0066] (Food and drink)

By blending the bone density increasing agent of the present invention into a food or drink as a raw material, a food or drink having an effect of increasing bone density can be obtained.

[0067] The form of the food for increasing bone density of the present invention is not particularly limited. For example, the food and drink are beverages, energy drinks, confectionery, processed foods, fats and oils, dairy products, retort foods, and range foods. Products, frozen foods, seasonings, health supplements, etc. The shape and properties are not particularly limited and can be solid, semi-solid, gel, liquid, powder, etc. Any of capsules, liquids, granules, etc. may be used. [0068] In addition, the food and drink for increasing bone density of the present invention may be blended with other physiologically active ingredients and the like for the purpose of improving various functions. Antioxidant ingredients, oily ingredients, various vitamins, minerals, amino acids, etc. for nutritional enhancement.

[0069] The antioxidant component is not particularly limited, but for example, tokovolols and their derivatives, tocotrienols and their derivatives, sesamin, epicesamine, sesaminol, sesamolin, sesamol and other lignans and their Glycosides, carotenoids such as β-carotene and their derivatives, tannins such as gallic acid ellagic acid and their derivatives, flavonoids such as flavone, catechin, quercetin, leucoanthocyanidin, ubiquinone, vitamin Κ, etc. Quinones, ferulic acid derivatives such as oryzanol, and olive extracts. There are no particular restrictions on the types of vitamins, minerals, amino acids, etc. that are used to enhance nutrition, but the ones specified in the Food Additives Regulations are desirable.

[0070] Specific examples of the food for increasing bone density according to the present invention are listed below, but the present invention is not limited thereto. In addition, there are no particular restrictions on the form, but for example, Japanese confectionery such as rice cakes, rice crackers, rice cakes, buns, rice cakes, cookies, biscuits, crackers, pie, castella, donuts, pudding, sponge cake, waffles, butter Cream, castor cream, cream puff, chocolate, chocolate confectionery, caramel, candy, chewing gum, jelly, hot cake, bread, confectionery and other Western confectionery, potato chip and other snacks, ice cream, popsicle, sorbet and other ice confectionery, Lactic acid beverages, lactic acid bacteria beverages, concentrated milk beverages, fruit juice beverages, pulp beverages, functional beverages, carbonated beverages and other soft drinks, green tea, tea, coffee, cocoa, and other beverages, fermented milk, processed milk Dairy products such as cheese, processed soybean foods such as soy milk and tofu , Jam, fruit syrup pickles, flower paste, peanut paste, fruit paste and other pastes, pickles, udon rice cakes, pasta and other cereal products, ham, sausage, bacon, dried sage, beef jerky, hamburger etc. Meat products, fish ham, fish sausage

, Power, fish and shellfish products such as maboko, chikuwa, hanpen, fish, dried fish such as shellfish, various species such as sea urchin, salmon, salmon, salted sea urchin, squid, etc. Salmon products such as salmon, paste, small fish, shellfish, wild vegetables, shiitake mushrooms, kelp, etc., retort food such as curry and stew, miso, soy sauce, sauce , Ketchup, bouillon, grilled meat sauce, curry sauce, stew sauce, soup sauce, soup stock, various seasonings such as soup stock, cooked rice, oil and fat, margarine, shortening, mayonnaise, dressing and other processed fats and oils Range, frozen foods, etc. containing

[0071] In particular, from the aspect of continuous intake, cooked rice, various seasonings, edible oils and fats and margarine

It can be said that processed oils and fats such as shortening, mayonnaise, dressing and the like are preferable.

[0072] Further, the shape and properties are not particularly limited, and any solid, semi-solid, gel, liquid, powder, etc. may be used. Soft force Capsule, liquid, granule, etc. filled and processed into capsules and hard capsules may be used.

[0073] When the bone density increasing agent of the present invention is added to food and drink, the bone density increasing agent is an oily component, and therefore, part or all of the oily component in each food and drink is replaced with a bone density increasing agent. It is preferable to combine them.

[0074] Specifically, edible oils and fats contain 95 to 100 mass%, margarine and shortening 70 to 80 mass%, mayonnaise 50 to 70 mass%, and dressing 10 to 30 mass% Can be made.

[0075] Further, 5-20% by mass can be contained in bread and confectionery, and 5-20% by mass can be contained in beverages.

[0076] (Display)

In the present invention, the indication that it is used for the prevention and improvement of osteoporosis is a notation that can be displayed mainly as a food for specified health use. For example, “a reduction in bone density is suppressed and osteoporosis is prevented. “To do it”, “To increase bone density and be healthy bones”, “Those who are concerned about osteoporosis”, and the like.

[0077] The indication that it is preferable to use in combination with exercise in the present invention is a notation that can be displayed mainly as food for specified health use. Examples include “Increase”, “Exercise after eating and drinking”, “If you want to increase bone density, exercise such as walking”.

[0078] It should be noted that it is preferable to use in combination with exercise. In addition to the indication that it is used for this purpose, the effect of increasing bone density becomes more prominent with exercise, so the indication that it is used for the prevention and improvement of osteoporosis described above is used in combination You can do it.

[0079] It should be noted that these indications can be attached to the container and packaging means by a conventionally known method, thereby clearly showing that the food and drink of the present invention are used for the prevention and improvement of osteoporosis. Therefore, the distinction from normal food and drink becomes clear.

Example

[0080] Next, the present invention will be further described with reference to examples, but the present invention is not limited to these examples.

[0081] [Example 1]

Example 1 shows the bone density of the femur bone of a rat fed with a diet containing a bone density increasing agent (medium chain fatty acid triglyceride, Nisshin Oiliognolep Co., Ltd., trade name: ODO (registered trademark)), This is a test in which la and rapeseed oil (manufactured by Nissin Oilio Group Co., Ltd.) containing medium-chain fatty acids was compared as a control feed. Tests were sacrificed 6 weeks of feeding after rats, the excised femoral measured bone density in bone densitometry apparatus DCS- 600EX- IIIR (Alok _a Inc.), was analyzed.

[0082] After 5-week-old Wistar male rats were preliminarily raised for 1 week, they were divided into 2 groups: a rapeseed oil-added group (control group) and a bone density increasing agent-added group. Experimental food and water based on AIN 93 standard feed (mass%) were given. During the test period, the body weight and food intake of rats were measured over time.

[0083] After completion of the test, blood of the rat was collected under anesthesia with Nembutal (Dainippon Pharmaceutical Co., Ltd.), the femur of the hind limb was removed, and the soft tissue was removed. The bone density was measured. In the analysis, the bone density was calculated by dividing the whole femur bone into the proximal part, the diaphysis part, and the distal part. The results are shown in Table 1.

[0084] [Table 1]

(Unit: mg / cm

*: p <0.05 vs rapeseed oil control group [0085] From Table 1 above, it was shown that the bone density in the bone density increasing agent-added group was significantly increased in the distal femur (site with a lot of cancellous bone) compared to the rapeseed oil added group. It was.

[0086] The onset of postmenopausal osteoporosis is frequently observed mainly in sites containing a large amount of cancellous bone due to lack of female hormones. The results show that the bone density of the distal femur, which is mainly composed of cancellous bone, increased significantly due to the intake of a bone density increasing agent containing medium chain fatty acid triglycerides as an active ingredient. It was suggested that may contribute to the prevention of osteoporosis.

[0087] In this example, rats in the growth phase (6 weeks to 12 weeks of age) were used, and the increase in bone density in the distal femur due to the intake of medium-chain fatty acid tridalylide reached the growth phase. The possibility of contributing to the increase in maximum bone mass was shown. Therefore, intake of bone mineral density increasing agents containing medium-chain fatty acid triglycerides as an active ingredient has a beneficial effect on bone growth and development compared to normal oil intake, and the risk of developing postmenopausal and senile osteoporosis. Is expected to reduce

[Example 2]

Example 2 is a study in which the effect of combined use of a bone density increasing agent and aerobic exercise on the bone density of growing rats was examined based on Example 1 described above.

[0089] 5-week-old Wistar male rats were preliminarily raised for 1 week before rapeseed oil (Nisshin Oilio Group)

(Supplied)) Addition group (control group), medium-chain fatty acid triglyceride (Nisshin Oillio Group, product name: ODO (registered trademark)) addition group, divided into 8 groups each, Based on AIN93 standard diet containing 12% (mass%) of fats and oils, experimental diet and water were given. For exercise load, a treadmill (manufactured by Natsume Seisakusho Co., Ltd.) was used, and a running exercise of 45 minutes at a speed of 20 m / min was performed 5 days a week (Monday to Friday). The maximum intensity of running in growing rats is approximately 40 m / min. In this example, rats were allowed to run at a speed of 50% of their maximum exercise intensity, that is, at a speed of 20 m / min. It can be said that this exercise intensity corresponds to human aerobic exercise. Body weight and food consumption were measured over time, and exercise and rearing were conducted for 6 weeks.

[0090] Rats subjected to the test after 6 weeks were blood-collected under anesthesia with Nembutal (Dainippon Pharmaceutical Co., Ltd.) in the same manner as in Example 1, the femur of the hind limb was removed, and the soft tissue was removed. The bone density of the femur was measured with a bone density measuring device. The analysis includes the entire femur and the proximal part, Each bone density was calculated by dividing into a diaphyseal part and a distal part. The results are shown in Table 2.

[0091] [Table 2]

(Single: mg / cm ²

*: p <0.05 vs rapeseed oil control exercise group

[0092] From Table 2 above, when used in combination with exercise, the thigh that is important in preventing osteoporosis shown in Example 1 compared to the rapeseed oil addition group in which the bone density increasing agent addition group is the control group A significant increase in bone density was observed not only in the distal bone but also in the whole bone.

[0093] As described above, ingestion of the bone density increasing agent comprising medium-chain fatty acid triglyceride as an active ingredient from Example 1 and Example 2 has a positive effect on the bone growth of rats in the growth phase, and exercise is also used in combination. In this case, the bone density was further increased, suggesting the combined effect of both.

[0094] [Example 3]

Example 3 is a verification test on the effect of the bone density increasing agent of the present invention on the bone density of human elderly PEM patients. Therefore, it should be performed on human PEM patients. However, PEM patients are weakened due to malnutrition and other reasons, and it is dangerous to allow such people to take new foods experimentally. In such a case, a method is generally used in which a disease model animal having symptoms similar to those of human PEM is prepared and evaluated using the animal.

[0095] In this study, a PEM model rat was prepared by feeding a rat with a low-protein diet containing the bone density increasing agent of the present invention, and the bone density of the rat was affected. The effect was investigated.

[0096] (PEM model rat)

Patients with PEM have a serum serum albumin level that is about 20% lower than that of normal humans. Therefore, in this study, when the serum albumin level test of a rat was reduced by 20% or more from the value at the start of the test, it was diagnosed that the rat developed PEM.

This time, PEM model rats were produced by administering a low-protein diet (test food), which will be described in detail later. Serum serum in control rats after administration of test meal When the rubmin value was examined, it decreased by 21.8% compared to the rat before administration of the test meal, confirming that a PEM model rat was produced.

[0097] (Method for Measuring Serum Albumin Level in Rat)

The BCG method was used as a method for measuring serum albumin levels. In this method, the concentration of albumin is determined by measuring the blue absorbance of albumin and bromtalesol green (BCG) bound in a test tube using a spectrophotometer. Widely used for diagnosis.

[0098] Specifically, a mixture of rat serum 5 μl and albumin coloring reagent (containing 37 mM succinate buffer ph4.2, BCGO. 08 mM) 1 ml was left at room temperature for 10 minutes, Absorbance at a length of 630 nm was measured. Next, the serum albumin value was calculated by comparison with the measured value of standard serum with a known concentration by the same method.

[0099] (Feeding to rats, production of PEM model rats)

Three weeks old Wistar male rats were preliminarily raised for 3 days, then rapeseed oil added group (control group), bone density increasing agent (medium chain fatty acid triglyceride, Nisshin Oiliognole Co., Ltd., trade name: ODO) added group The two groups were divided into 10 groups each, and feed and water having the composition shown in Table 3 were given. The feed was based on the AIN93 standard feed, and the protein source casein was reduced from 20% to 5% by weight, and the amount was replaced with —starch. During the breeding period, there was no particular exercise load such as running exercise with a treadmill, and the animals were raised individually in stainless steel mesh cages and allowed to act freely.

[0100] On the 4th week after administration of the test diet, blood of the rat was collected under ether anesthesia, and this was centrifuged to prepare serum. Serum albumin level was measured by BCG method.

[0101] The serum albumin level of the rats before administration of the test meal was also measured. Table 4 shows the results.

[0102] [Table 3] Feed composition (mass%)

Ingredients Feed for control group Rat feed for rats with bone density increasing agent β Corn starch 5 4. 7 5 5 4. 7 5

Corn starch 1 3. 2 0 1 3. 2 0

Sucrose 1 0. 0 0 1 0. 0 0

Casein 5. 0 0 5. 0 0

Senorelose powder 5. 0 0 5. 0 0

Mineral mixing 3.5 5 3. 5 0

Mixing vitamins 1. 0 0 1. 0 0

L Cystine 0. 3 0 0. 3 0

Choline bitartrate 0. 2 5 0. 2 5

Rapeseed oil 7. 0 0 0. 0 0

Bone density increasing agent 0. 0 〇 7. 0 0

A □ = Port 4- Γ 1 0 0. 0 0 1 0 0. 0 0

[0103] [Table 4]

Note 1: Significantly different from the rapeseed oil control group (P <0. 0 5)

[0104] From the results shown in Table 4, when the low-protein diet was ingested, the control group of rats had a serum albumin level S decreased by 21.8% compared to the rats before administration of the test meal. , P

He developed EM and became a PEM model rat.

[0105] On the other hand, in the bone density increasing agent-added group fed with a low-protein diet, the serum albumin level S was decreased by only 14.0% compared to the rat before administration of the test meal.

Found that PEM has not developed.

[0106] (Bone density measurement test)

Rats were sacrificed after 4 weeks of breeding, and the excised femur was measured using a bone densitometer DCS-600EX

by measuring the bone density in the _niR (Alok _a Co., Ltd.), it was analyzed.

[0107] Further, after removing the femoral bone of the hind limb and removing the soft tissue, the bone density was measured with the above-described bone density measuring apparatus. In the analysis, the bone density was calculated by dividing the entire femur and the proximal, diaphyseal, and distal parts. The results are shown in Table 5.

[0108] [Table 5] Bone density value (unit: mg / cm ² )

Total bone density Proximal bone density Stem bone density Distal bone density Control group 7 7. 1 ± 0. 9 8 0. 6 ± 1. 2 6 6. 6 ± 1. 5 8 9. 0 ± 1. 0 Bone density

8 1. 0 ± 1. 2 8 6. 6 ± 2. 3 7 1. 0 ± 1. 3 9 3. 1 ± 0. 7 Increaser

(Note 2) (Note 2) (Note 2) (Note 3) Additive group

Note 2: Significantly different from the rapeseed oil control group (p <0. 0 5)

Note 3: Significantly different from the rapeseed oil control group (p <0. 0 1)

[0109] From the results shown in Table 5, the bone density increasing agent-added group showed a significant increase in bone density at all measured sites compared to the rapeseed oil added group. It was found that the increase was remarkable in the distal femur, which is an important site for prevention of the disease.

[0110] From the above experimental results, by taking a bone density increasing agent containing medium-chain fatty acid triglycerides as an active ingredient, hypoalbuminemia, which is a symptom of PEM, was observed compared to intake of vegetable oil (rapeseed oil). It was found that there is a possibility of reducing the risk of developing osteoporosis, which can prevent bone fracture that can cause PEM.

Claims

The scope of the claims

[1] A bone density increasing agent comprising a medium chain fatty acid and Z or a acyl glycerol containing a medium chain fatty acid as an active ingredient.

2. The bone density increasing agent according to claim 1, wherein the medium chain fatty acid is a fatty acid having 6 to 12 carbon atoms.

[3] The bone density increasing agent according to claim 1 or 2, wherein the acyl glycerol containing the medium chain fatty acid is a medium chain fatty acid triglyceride.

[4] A food or drink containing the bone density increasing agent according to any one of claims 1 to 3.

[5] The food or drink according to claim 4, which is labeled for use in preventing or improving osteoporosis.

[6] The food or drink according to claim 4 or 5, wherein the food or drink is marked with an indication that it is preferable to use it together with exercise.

[7] A method of using a medium chain fatty acid and / or a acyl glycerol containing a medium chain fatty acid for producing a bone density increasing agent.

[8] An osteoporosis-preventing agent comprising medium-chain fatty acid and / or acylglycol containing medium-chain fatty acid as an active ingredient.

[9] A therapeutic agent for osteoporosis comprising a medium chain fatty acid and Z or a acyl glycerol containing a medium chain fatty acid as an active ingredient.