Method for producing osteocalcin-containing composition and osteocalcin-containing composition

Abstract

To provide a method for producing an osteocalcin-containing composition and the like, which makes it possible to increase the absolute quantity of Glu type absorbed as an active constituent with reduced cost.SOLUTION: A method for producing an osteocalcin-containing composition includes an acid treatment step of subjecting a raw material containing osteocalcin to acid treatment. This enables production of an osteocalcin-containing composition with a higher ratio of Glu type.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing an osteocalcin-containing composition and an osteocalcin-containing composition. [Background technology]

[0002] Osteocalcin (OC) is a non-collagenous protein present in bones of humans, pigs, etc., accounting for approximately 0.4% of the total. It is secreted by osteoblasts, which are bone-forming cells. While it is expected to have so-called "rejuvenating" effects, including increased cognitive function and improved reproductive ability, it has not yet become widespread on the market due to the difficulty of mass production.

[0003] In this regard, the present inventors have invented a technology that reduces membrane trouble during concentration in the production of osteocalcin-containing compositions and that leads to mass production (Patent Document 1).

[0004] Osteocalcin is composed of two molecular forms: the stable OCGla (hereinafter referred to as "Gla type") and the active OCGlu (hereinafter referred to as "Glu type"). The Glu type has recently been shown to be effective in metabolism, and much research has been conducted on it. For example, it has been reported that the Glu type contributes to the expansion of insulin-secreting β cells, the inhibition of cancer cell proliferation, the reduction of hypertrophic fat, the improvement of cellular antioxidant properties, the improvement of visceral function, and the improvement of bone mineral density (Non-Patent Documents 1-3). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 7390158 [Non-patent literature]

[0006] [Non-Patent Document 1] Yoshikazu Hayashi, "Analysis of the mechanism of cancer cell proliferation inhibition by osteocalcin," Kyushu University, 2016 [Non-patent document 2] Takahito Otani, "Functional activation of adipocytes by osteocalcin", Kyushu University, 2014 [Non-patent document 3] Teruhiko Kondo, "The effect of osteocalcin on the progression of arteriosclerosis and the development of lifestyle-related diseases in the next generation," Kyushu University, 2017 Summary of the Invention [Problem to be solved by the invention]

[0007] However, in normal osteocalcin, the Gla type accounts for approximately 95% and the active ingredient, Glu type, accounts for only about 5%. Furthermore, increasing the concentration of osteocalcin is costly, and there is a lot of waste, as the Gla type, which is not an active ingredient, still accounts for the majority of the osteocalcin.

[0008] Therefore, an object of the present invention is to provide a method for producing an osteocalcin-containing composition that can increase the absolute amount of Glu-type osteocalcin absorbed as an active ingredient while keeping costs low. [Means for solving the problem]

[0009] A first aspect of the present invention is a method for producing an osteocalcin-containing composition, which includes an acid treatment step of treating a raw material containing osteocalcin with an acid.

[0010] A second aspect of the present invention is the method for producing an osteocalcin-containing composition according to the first aspect, wherein the acid treatment step involves acid-treating the raw material using an acidic solution having a pH of 1 or more and 5 or less.

[0011] A third aspect of the present invention is the method for producing an osteocalcin-containing composition according to the first aspect, wherein the acid treatment step involves acid-treating the raw material using an acidic solution having a pH of 1 or more and 4 or less.

[0012] A fourth aspect of the present invention is the method for producing an osteocalcin-containing composition according to the second or third aspect, wherein the acidic solution contains hydrochloric acid.

[0013] A fifth aspect of the present invention is the method for producing an osteocalcin-containing composition according to the fourth aspect, wherein the acidic solution further contains either sulfuric acid, citric acid, or citric acid and trisodium citrate.

[0014] A sixth aspect of the present invention is the method for producing an osteocalcin-containing composition according to the first aspect, further comprising an enteric encapsulation step of encapsulating the composition that has been subjected to the acid treatment step in an enteric capsule.

[0015] A seventh aspect of the present invention is an osteocalcin-containing composition, in which the ratio of the Glu-type concentration to the total osteocalcin concentration is 10% or more.

[0016] An eighth aspect of the present invention is the osteocalcin-containing composition according to the seventh aspect, which is contained in an enteric capsule. [Effects of the Invention]

[0017] According to each aspect of the present invention, it is possible to produce a composition containing osteocalcin with an increased proportion of Glu-type osteocalcin, which makes it possible to obtain better metabolic effects than conventional methods, in which the Glu-type has been shown to contribute as an active ingredient.

[0018] Furthermore, according to any one of the second to fifth aspects of the present invention, it becomes possible to effectively promote the reaction from Gla type to Glu type.

[0019] Here, taking into consideration that a portion of the Gla type is converted to the Glu type by gastric acid, it may be considered better not to encapsulate the osteocalcin-containing composition in an enteric capsule.

[0020] However, based on the finding that osteocalcin may be degraded by digestive enzymes in the stomach, the sixth or eighth aspect of the present invention prevents the Glu-type from being degraded in the stomach, enabling the Glu-type contained in the enteric-coated capsule to be absorbed in the intestine without reducing its absolute amount. This is a meaningful concept, as the present invention makes it possible to pre-adjust the desired absolute amount of the Glu-type. DETAILED DESCRIPTION OF THE INVENTION

[0021] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. However, the present invention is not limited to the following examples. [Example]

[0022] An aqueous solution containing osteocalcin extracted from pig bone pellets with an alkaline solution containing sodium bicarbonate and calcium carbonate was stirred for 24 hours. The extracted solution was diluted with water and a solution desalted using an ultrafiltration membrane (UF membrane) to a pH of approximately 7. Dilute hydrochloric acid was then added to the mixture to adjust the pH to 3 or less, and the mixture was allowed to stand for approximately 1 hour. For example, a 6% concentration of dilute hydrochloric acid can be used.

[0023] The results, as shown in Table 1, demonstrated a significant increase in the proportion of Glu-type osteocalcin. In particular, when comparing the alkaline range of pH 9 and the neutral range of pH 7 with the acidic range of pH 3-5, the proportion of Glu-type osteocalcin increased approximately six-fold (from approximately 5% to approximately 30%), while the proportion of Gla-type osteocalcin decreased from approximately 95% to approximately 70%. The fact that the total osteocalcin concentration at pH 7 was higher than at other pH levels is likely due to measurement error. In any case, it was confirmed that it is possible to significantly increase the proportion of Glu-type osteocalcin by at least making the sample acidic.

[0024] [Table 1]

[0025] Although a pH range of 1 to 5 has been shown to be effective, considering the ease of acid treatment, a pH of 1 to 4 is preferred. Furthermore, a pH of 2 to 4 is even more preferred in view of increasing the proportion of Glu type.

[0026] The acid solution used in the acid treatment is preferably hydrochloric acid, but other acid solutions such as sulfuric acid, citric acid, or a solution containing trisodium citrate, or a mixture of these may also be used.

[0027] When the osteocalcin-containing composition of the present invention, in which the proportion of Glu-type osteocalcin has been increased, is orally ingested, it is preferably placed in an enteric capsule.

[0028] When a composition containing osteocalcin is orally ingested, it is thought that the reaction from Gla to Glu is promoted by gastric acid in the stomach, but digestive enzymes also cause osteocalcin to be broken down, resulting in a decrease in the absolute amount of osteocalcin, including the Glu form.

[0029] Therefore, by placing it in an enteric-coated capsule, a composition containing osteocalcin with a high proportion of Glu-type can be delivered to the intestine without being degraded by digestive enzymes in the stomach, making it easier to absorb a desired amount of Glu-type from the intestine.

[0030] Although osteocalcin other than porcine osteocalcin may be used as the material, porcine osteocalcin is preferable from the viewpoint of its affinity with the human body and the possibility of mass production.

Claims

1. A method for producing an osteocalcin-containing composition, comprising: A method for producing an osteocalcin-containing composition, comprising an acid treatment step of treating a raw material containing osteocalcin with an acid.

2. 2. The method for producing an osteocalcin-containing composition according to claim 1, wherein the acid treatment step comprises acid-treating the raw material using an acidic solution having a pH of 1 to 5.

3. 2. The method for producing an osteocalcin-containing composition according to claim 1, wherein the acid treatment step comprises acid-treating the raw material using an acidic solution having a pH of 1 to 4.

4. The method for producing an osteocalcin-containing composition according to claim 2 or 3, wherein the acidic solution contains hydrochloric acid.

5. 5. The method for producing an osteocalcin-containing composition according to claim 4, wherein the acidic solution further contains either sulfuric acid, citric acid, or citric acid and trisodium citrate.

6. 2. The method for producing an osteocalcin-containing composition according to claim 1, further comprising an enteric encapsulation step of encapsulating the composition that has been subjected to the acid treatment step in an enteric capsule.

7. An osteocalcin-containing composition, in which the proportion of Glu type concentration in the total osteocalcin concentration is 10% or more.

8. 8. The osteocalcin-containing composition according to claim 7, which is contained in an enteric capsule.

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