KR102555277B1 - Composition for stimulating osteogenesis or preventing bone loss - Google Patents

Abstract

The composition for promoting bone formation or preventing bone loss of the present invention includes organic whole milk powder (OMP) and colostrum basic protein (CBP), wherein the colostrum basic protein is separated from colostrum from 1 to 10. It is a protein with a molecular weight of 30 kD.

Description

Composition for promoting bone formation or preventing bone loss {Composition for stimulating osteogenesis or preventing bone loss}

The present invention relates to a composition for promoting bone formation or preventing bone loss. Specifically, the present invention increases the production of osteocalcin and activates osteoblasts to promote bone formation and suppresses the differentiation of osteoclasts to prevent bone loss and increase bone formation, resulting in excellent bone formation promoting effects even when bone growth is limited. It relates to a composition that can provide.

In recent years, the growth and development of children and adolescents has been greatly increased in our society due to westernization of eating habits and improvement of nutritional status, and most people have a lot of interest in growth as a social atmosphere favoring tall height is formed.

In order to promote growth, growth hormone administration method, Illizanov surgery method, health supplement intake method, etc. have been used, but the growth hormone administration method has a problem that it can cause various side effects, and the Ilizanov surgery method There are problems with the risk of surgery, the pain and cost burden of surgery, and the way to take health supplements has a problem that most health supplements are not scientifically verified or are ineffective.

In order to solve this problem, Korean Patent Registration No. 10-0509681 discloses a food composition containing an isolated whey fraction derived from colostrum or milk of a mammal and having an activity that can effectively promote growth without side effects.

The present inventors attempted to provide a more effective composition for promoting bone formation by utilizing these technologies, and based on the results of related interim studies, the inventors also recognized the possibility of a bone loss preventive effect, which would help with problems related to bone loss such as osteoporosis. A composition that can also be provided.

Korean Patent Registration No. 10-0509681

An object of the present invention is to provide a composition having excellent effects in promoting bone formation or preventing bone loss, and in particular, with respect to the proliferation of osteoblasts and the activation of growth factors, it is helpful in bone activation, promotion of bone formation, and prevention of bone loss. It is to provide a composition that is.

According to one aspect of the present invention, the present invention is a composition for promoting bone formation or preventing bone loss, comprising organic milk powder and colostrum basic protein, wherein the colostrum basic protein is a protein having a molecular weight of 1 to 30 kD isolated from colostrum. provides

The composition of the present invention can prevent bone loss by increasing the production of osteocalcin, activating osteoblasts to promote bone formation, and inhibiting the differentiation of osteoclasts. In particular, the composition of the present invention can provide an excellent bone formation promoting effect even when bone growth is restricted.

1 shows a schedule of animal experiments to confirm the effect of promoting bone formation and preventing bone loss of the composition of the present invention.
2 to 8 show the results of animal experiments provided with a composition according to an embodiment of the present invention.
Figure 2 shows the change in body weight of the experimental animals.
Figure 3 shows the feed intake of the experimental animals.
Figure 4 shows the weight of the femur of the experimental animals (OVX group).
Figure 5 shows the content of osteocalcin in the blood of experimental animals (OVX group).
Figure 6 shows the serum BAP concentration of experimental animals (OVX group).
7 (OVX group) and 8 (Sham group) show TRAP activity in the blood of experimental animals. [Control (or Con), basic feed group; CBP, colostrum basal protein (CBP)-containing feed group; CBP+OMP, Colostrum Basic Protein (CBP) and Organic Milk Powder (OMP) Combination Feeding Group; OVX, ovariectomy group; Sham and the OVX group performed the same operation, but the ovaries were not resected.]

The composition of the present invention is characterized by comprising organic whole milk powder (OMP) and colostrum basic protein (CBP).

The composition of the present invention can increase the production of osteocalcin by combining organic milk powder and colostrum basic protein, promote bone formation by activating osteoblasts, and suppress bone loss by inhibiting the differentiation of osteoclasts. In particular, even when bone growth is limited, an excellent bone formation promoting effect can be provided.

The composition of the present invention may exhibit a synergistic effect according to the combination of organic milk powder and colostrum basic protein.

In the present invention, the colostrum basal protein refers to a protein having a molecular weight of 1 to 30 kD isolated from colostrum, that is, colostrum basal protein, and can be obtained, for example, using an ultrafiltration membrane. As a specific example, the basic colostrum protein can be obtained by passing colostrum through a 30 kD ultrafiltration membrane to obtain a filtrate, and passing the filtrate through a 1 kD ultrafiltration membrane to obtain a residue.

Colostrum generally means milk up to 5 days after parturition, and in the present invention, colostrum is preferably milk up to 4 days after parturition, more preferably milk up to 3 days after parturition, more preferably 2 days after parturition. milk until In one specific embodiment, the colostrum is bovine (eg, cow's milk) colostrum.

In one specific embodiment, the colostrum basal protein (CBP) is free of alpha-lactalbumin and beta-lactoglobulin. Removal of alpha-lactalbumin and beta-lactoglobulin can be achieved through a protein separation method known in the art, for example, a separation method using an isoelectric point. Alpha-lactalbumin and beta-lactoglobulin are preferably removed through pH adjustment and precipitation.

In a preferred embodiment, the colostrum basic protein is a whey isolate fraction disclosed in Korean Patent Registration No. 10-0509681 (the entirety of which is incorporated herein by reference).

In the present invention, the organic milk powder is fed organically produced feed without using chemical fertilizers or pesticides for, for example, for 1 year, preferably for 2 years or more, more preferably for 3 years or more, and grazing without using antibiotics. It may be from an animal (e.g., a dairy cow) raised healthy in an environment where this is possible.

The composition of the present invention may contain organic milk powder and colostrum basic protein in varying degrees. In one embodiment, the composition of the present invention comprises 0.1 to 10 parts by weight of colostrum basic protein based on 100 parts by weight of organic milk powder to promote bone formation or prevent bone loss through osteoblast activation and osteoclast differentiation inhibition. More preferably, it contains 0.2 to 5 parts by weight of colostrum basic protein based on 100 parts by weight of organic milk powder, and more preferably contains 0.5 to 2 parts by weight of colostrum basic protein based on 100 parts by weight of organic milk powder.

In one embodiment, the composition of the present invention contains organic milk powder at 1% by weight or more and colostrum basic protein at 0.01% by weight or more to promote bone formation or prevent bone loss through osteoblast activation and osteoclast differentiation inhibition. include More preferably, it contains 5% by weight or more of organic milk powder and 0.05% by weight or more of colostrum basic protein. More preferably, it contains 7% by weight or more of organic milk powder and 0.07% by weight or more of colostrum basic protein. More preferably, it contains 8% by weight or more of organic milk powder and 0.08% by weight or more of colostrum basic protein. More preferably, it contains 9% by weight or more of organic milk powder and 0.09% by weight or more of colostrum basic protein.

In one embodiment, the composition of the present invention is a food composition. In addition, it can be used as a feed for promoting bone formation or preventing bone loss in mammals other than humans.

The composition of the present invention may further include a food-acceptable material together with organic milk powder and colostrum-based protein. For example, it may further include carbohydrates, proteins, minerals, vitamins, etc., but is not limited thereto. Compositions of the present invention may be in a variety of forms. For example, it may be in the form of powder, granule, tablet or capsule, and in addition, processed meat products, fish products, tofu, jelly, porridge, noodles such as ramen or noodles, seasonings such as soy sauce, soybean paste, red pepper paste, and mixed paste , sauces, confectionery, milk products such as fermented milk or cheese, pickled foods such as kimchi or pickles, fruits, vegetables, soy milk, and beverages such as fermented beverages, but may be in the form of food, but are not limited thereto.

In one embodiment, the composition of the present invention further comprises 1 to 10 parts by weight of fructooligosaccharide based on 100 parts by weight of the organic milk powder.

In one embodiment, the composition (eg, food composition) of the present invention comprises 90% by weight or more of organic milk powder and 0.1% to less than 1% by weight of colostrum basic protein, and further contains vitamins, minerals and lactic acid bacteria. do.

In one embodiment, the composition (eg, food composition) of the present invention is a composition for promoting bone formation or preventing bone loss in growing children.

When the composition of the present invention is used as a feed, it may further include materials usable as a feed together with organic milk powder and colostrum-based protein. For example, it may further include grain, vegetable protein feed, animal protein feed, and sugar, but is not limited thereto. The composition of the present invention may be a feed composition for mammals, such as dogs, cats, cows, horses, pigs or goats, but is not limited thereto.

Hereinafter, the present invention will be described in more detail through examples. The following examples are intended to illustrate the present invention only, and the scope of the present invention is not to be construed as being limited thereto.

Example 1

(1) Colostrum Basic Protein (CBP)

Separated whey fractions according to the method disclosed in Korean Patent Registration No. 10-0509681 were used.

The manufacturing method of this whey separated fraction is specifically as follows.

Colostrum secreted from cows for 48 hours after parturition is collected and then centrifuged to remove the cream layer to obtain defatted colostrum. 1N hydrochloric acid was added to the defatted colostrum to adjust the pH to 4.6 to coagulate casein, and then centrifuged to obtain supernatant, colostrum whey. 1.5M trisodium citrate was added to the separated whey to adjust the pH to 5.5, and 1.5M citric acid was added to adjust the pH to 3.9, followed by heating at 35°C for 150 minutes to obtain alpha- Precipitates lactalbumin. It is centrifuged to remove alpha-lactalbumin and the supernatant is recovered. 1N NaOH was added to the supernatant to adjust the pH to 4.5 to precipitate beta-lactoglobulin, and the supernatant was obtained by centrifugation. The obtained supernatant was passed through a 30kD (kilodalton) ultrafiltration membrane to obtain a filtrate, and then the filtrate was again passed through a 1kD ultrafiltration membrane to obtain a residue. The residue is lyophilized to obtain an isolated whey fraction having a molecular weight of 1 to 30 kD in powder form.

(2) Organic Milk Powder (OMP)

Organic raw milk milked from cows was sterilized at about 72 ° C. for about 15 seconds, then quenched, and after checking the presence of foreign substances, it was homogenized using a fine mesh. After drying the homogenized raw milk and confirming whether metal was detected, organic milk powder was obtained.

(3) Feed mix

The feed was formulated by including the CBP of (1) and the OMP of (2) above.

Specific feed formulations are shown in Table 1.

[Table 1]

Comparative Examples 1 and 2

The feed was formulated in the same manner as in Example 1, but the feed was formulated according to Table 2 (Comparative Example 1), which is a basic feed formulation excluding CBP and OMP, or Table 3 (Comparative Example 2), a feed formulation excluding OMP. did

[Table 2]

[Table 3]

Experimental Example 1

A 24-week-old Sprague-Dawley (SD) rat model was used. An OVX group in which osteoporosis was induced by ovariectomy and bone growth was restricted was placed, and a Sham group was placed separately in some cases.

In detail, a control group (Control, Con) feeding the feed (basic feed) of Comparative Example 1 not containing CBP and OMP and CBP+ feeding the feed of Example 1 containing 0.1% CBP and 10% OMP It was divided into OMP groups, and in some cases, a CBP group fed with the feed of Comparative Example 2 containing 0.1% CBP was added.

After undergoing a recovery period of 3 weeks after surgery and an adaptation period of 1 week thereafter, the experimental schedule was followed by feeding the corresponding feed for each group for 4 weeks (FIG. 1). Feed was ad libitum once a week.

Body weight and feed intake were measured once a week.

After the experiment schedule was over, the left femur was extracted and its weight was checked.

Serum osteocalcin and serum BAP (bone alkaline phosphatase), serum osteoclast-related factors, and serum TRAP (tartrate-resistant acid phosphatase), which are serum osteoclast-related factors, were analyzed using ELISA (enzyme-linked immunosorbent assay) analysis method .

Bone microstructural indices such as bone mineral density, trabeculae thickness, trabeculae number, bone marrow area, average cortical bone thickness, etc. (Table 4) was analyzed.

[Table 4]

(2) Experimental results

○ Body weight and feed intake: There was an increase in body weight according to the OVX procedure, but there was no difference in body weight by CBP and OMP levels (0.1%, 10%) in both the OVX group and the Sham group (FIG. 2). There was no statistically significant difference in dietary intake (Fig. 3).

○ Bone weight: In the OVX group, unlike the CBP group, the weight of the femur increased in the CBP+OMP group compared to the control group (FIG. 4). This means that the composition in which CBP and OMP are combined has an effect of increasing bone weight, unlike the CBP alone composition.

○ Factors related to osteoblast and osteoclast

- Osteocalcin : Osteocalcin is a protein that binds calcium and bone matrix and has specificity for bone and dentin. Because it is produced in osteoblasts, it is a factor that can determine the activity of osteoblasts. As a result of the experiment, in the OVX group, the concentration of serum osteocalcin increased significantly in the CBP+OMP group compared to the CBP group (FIG. 5). This means that the composition in which CBP and OMP are combined has an effect of further increasing the production of osteocalcin and further activating osteoblasts compared to the composition of CBP alone.

- BAP (bone alkaline phosphatase) : BAP is a representative enzyme whose expression and activity increases during the differentiation process of osteoblasts, and is a factor that measures the differentiation of osteoblasts. As a result of the experiment, in the OVX group, compared to the control group, the concentration of serum BAP increased in both the CBP group and the CBP+OMP group (FIG. 6). This means that the composition in which CBP and OMP are combined, including the CBP alone composition, also has the effect of increasing the production of BAP and activating osteoblasts.

- TRAP (tartrate-resistant acid phosphatase) : TRAP is a highly expressed factor in osteoclasts whose activity decreases depending on the degree of differentiation of osteoclasts. As a result of the experiment, in the OVX group, there was no significant difference between the control group, CBP group, and CBP + OMP group (FIG. 7), but in the case of the Sham group, compared to the control group and CBP group, the concentration of serum TRAP in the CBP + OMP group was significantly decreased (FIG. 8). This means that the composition in which CBP and OMP are combined has an effect of significantly inhibiting the differentiation of osteoclasts compared to the CBP alone composition.

○ Bone microstructure index

As a result of analyzing the bone microstructural indices of the OVX group, it was found that the cortical bone area and intimal circumference increased in the group ingesting CBP+OMP compared to the control group, resulting in an increased degree of bone formation (Table 5).

[Table 5]

(Effect of CBP and OMP supplementation on femur bone parameters in OVX group)

Summarizing the above experimental results, it was found that the combination of CBP and OMP can promote bone formation by activating osteoblasts and prevent bone loss by inhibiting the differentiation of osteoclasts. In particular, it was found that the combination of CBP and OMP can provide more excellent effects in promoting bone formation or preventing bone loss by further activating osteoblasts and further suppressing the differentiation of osteoclasts compared to the control group.

manufacturing example

A food composition was prepared with the composition shown in Table 6 below.

[Table 6]

Claims (8)

Contains organic whole milk powder (OMP) and colostrum basic protein (CBP),
The colostrum basic protein is a protein having a molecular weight of 1 to 30 kD isolated from colostrum,
Based on 100 parts by weight of the organic milk powder, the colostrum basic protein is 0.2 to 5 parts by weight,
Containing 5% by weight or more of the organic milk powder,
A composition for promoting bone formation or preventing bone loss. delete According to claim 1,
The colostrum-based protein is separated from bovine colostrum, a composition for promoting bone formation or preventing bone loss. According to claim 1,
The colostrum-based protein is alpha-lactalbumin and beta-lactoglobulin is removed, a composition for promoting bone formation or preventing bone loss. According to claim 1,
1 to 1 fructooligosaccharide based on 100 parts by weight of the organic milk powder
A composition for promoting bone formation or preventing bone loss, further comprising 10 parts by weight. According to claim 1,
The composition is a food composition, a composition for promoting bone formation or preventing bone loss. According to claim 1,
The composition is based on 90% by weight or more of organic milk powder and colostrum
Contains 0.1% by weight or more and less than 1% by weight of protein,
Examples of promoting bone formation or bone loss, further including vitamins, minerals and lactobacilli
Composition for room. According to claim 1,
The composition is a composition for promoting bone formation or preventing bone loss in growing children.
water.

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