JP7353627B2 - Method for producing HMBCa powder composition - Google Patents

Description

The present invention relates to a method for producing an HMBCa powder composition having spherical crystals .

HMB (bis-3-hydroxy-3-methylbutyrate monohydrate) is a metabolite of leucine, which is a type of essential amino acid. HMB has generally been confirmed to have the effect of activating muscle protein synthesis and inhibiting its degradation. Therefore, HMB is used as a raw material for health foods, and in particular, powdered HMBCa hydrate is used as a raw material for preparations such as tablets and capsules, and supplements.

HMB is typically produced by an oxidation reaction between diacetone alcohol and sodium hypochlorite. HMB, which has a relatively low reaction yield, is then subjected to extraction and purification steps to increase its purity. Powdered HMBCa hydrate is obtained by adding a calcium salt such as calcium hydroxide to a solution of HMB to produce HMBCa, which is then subjected to shelf drying, pulverization, sieving, etc. to form a powder. When manufacturing pharmaceutical preparations and supplements, they are compressed into tablets using a tablet machine, for example. Alternatively, it is filled into hard capsules using a filling machine to form capsule tablets. Generally, powder raw materials are required to have fluidity for tabletting or filling, but the fluidity of conventional powdered HMBCa hydrates has not been sufficient. As a result, the mass of the tablets may vary or the finish may be poor. Particularly in the case of direct tabletting, which requires fluidity, tabletting is actually impossible.

As one countermeasure, mixing auxiliary raw materials to increase fluidity has been considered, but this is uneconomical. Therefore, the appearance of a powdered HMBCa hydrate with improved fluidity has been desired, but this has not yet been achieved.

Japanese Patent Application Publication No. 2018-145121 Special table 2014-525410 publication Japanese Patent Application Publication No. 2015-218158 Special Publication No. 2016-514733 Patent No. 6470481 Special table 2014-525410 publication Special table 2014-506254 publication

The present invention has been made based on such circumstances, and an object thereof is to provide a method for producing an HMBCa powder composition that can obtain an HMBCa powder composition with improved fluidity.

Furthermore, another object of the present invention is to provide a method for producing an HMBCa powder composition that is suitable as a raw material for preparations such as tablets and capsules, and supplements.

The method for producing the HMBCa powder composition of the present invention includes the steps of: preparing a solution containing HMBCa by dissolving HMBCa hydrate having needle-like crystals; and spray-drying the solution containing HMBCa to form crystals. and obtaining a spherical HMBCa hydrate. The HMBCa powder composition according to a preferred embodiment contains HMBCa (calcium 3-hydroxy-3-methylbutyrate) hydrate as a main component, has spherical crystals, an angle of repose of 35° or less, and an apparent density of 0. It is 5 g/ml or more. Preferably, the angle of repose is 30° or less and the apparent density is 0.54 g/ml or more.

1 is a chemical formula of HMBCa hydrate constituting the HMBCa powder composition according to an embodiment of the present invention. 1 is a list showing the results of the crystal system, angle of repose, and apparent density of each HMBCa powder of Examples 1 to 6 and Comparative Examples 1 to 9. 1 is a micrograph of HMBCa powder of Example 1. 3 is a micrograph of HMBCa powder of Example 2. 3 is a micrograph of HMBCa powder of Example 3. 1 is a micrograph of HMBCa powder of Comparative Example 1. 3 is a micrograph of HMBCa powder of Comparative Example 2. 3 is a micrograph of HMBCa powder of Comparative Example 7.

Hereinafter, a method for producing an HMBCa powder composition according to a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings. However, the technical scope of the present invention is not interpreted to be limited in any way by the embodiments described below.

The HMBCa powder composition according to the embodiment is a powder whose main component is a hydrate of HMB calcium (HMBCa; calcium 3-hydroxy-3-methylbutyrate). Hereinafter, a powder containing HMBCa hydrate as a main component may be referred to as "HMBCa powder". Moreover, FIG. 1 shows an example of notation of the chemical formula of HMBCa hydrate. HMBCa hydrate is, for example, a monohydrate (n=1). In addition, "consisting as a main component" means that the content of HMBCa is, for example, 90% by mass or more, preferably 98% by mass or more, on a dry basis.

The crystal system of HMBCa powder is spherical in this embodiment, whereas the crystal system of conventional HMBCa powder is acicular. Whether the crystals are spherical or acicular can be confirmed by microscopic photographs, etc., as is clear from the results of Examples described later. The average particle diameter of the spherical crystals is preferably 100 μm or less.

The angle of repose of the HMBCa powder is 35° or less, preferably 30° or less, and the apparent density of the HMBCa powder is 0.5 g/ml or more, preferably 0.54 g/ml or more. The angle of repose is the angle between the powder layer surface and the horizontal plane when the powder is deposited in a gravitational field to form a free surface. As an example of the measurement method, according to JIS R 9301-2-2, HMBCa powder is freely fallen from above onto a horizontal surface of a certain area using a funnel etc. to form a conical deposited layer, and the conical surface and horizontal surface are An injection method is used to measure the angle between the Moreover, apparent density is the mass per unit volume of powder, and is synonymous with "bulk specific gravity." As an example of a measurement method, in accordance with JIS K 3362, HMBCa powder is allowed to fall freely into a container from above using a funnel, the bulk volume and mass of the HMBCa powder in the container are measured, and the apparent density is calculated by calculation. .

An example of a method for manufacturing such HMBCa powder will be explained. First, HMBCa hydrate as a raw material is prepared. HMBCa hydrate can be produced by a known method. That is, HMBCa is produced by adding a calcium salt such as calcium hydroxide to HMB produced using diacetone alcohol and sodium hypochlorite as raw materials, and a drying process by shelf drying, a pulverizing process, and a sieving process are obtained. This is a powdered HMBCa hydrate produced by Of course, it may be manufactured by other methods. Alternatively, a commercially available powdered HMBCa hydrate may be used. It has been confirmed that all of these have needle-like crystal systems.

Next, the raw material HMBCa hydrate is dissolved in water, preferably hot water, and undissolved residues and the like are removed by filtration using a filtration device such as a filter press or a cartridge filter. As the filter medium, one having a filtration accuracy of 0.5 μm to 5 μm is used, for example. The filtrate is then dried by spray drying to obtain HMBCa powder according to embodiments. The HMBCa-containing solution produced in the reaction step in the above-mentioned known production method cannot be spray-dried, so it is dried on a shelf. Spray Drying Spray drying was made possible by dissolving the hydrate in warm water and preparing a solution. As is clear from the results of the Examples described later, the HMBCa powder obtained by spray drying has spherical crystals, an angle of repose of 35° or less, and an apparent density of 0.5 g/ml or more. Further, the HMB content in 100 parts by mass of HMBCa is 85% by mass or more, and the Ca content in 100 parts by mass of HMBCa is 14% by mass or more.

The obtained HMBCa powder is used, as a preferred example, as a raw material for health foods. Among them, there are tablets such as tablets and capsules. Tablets are formed, for example, by adding additives such as excipients, binders, and disintegrants, or other functional ingredients to HMBCa powder, and then compressing the mixture with a tablet machine. The tableting method may be either a direct tableting method in which the tablet is compressed as it is or a granule tableting method in which the tablet is made into granules and then compressed. On the other hand, capsule tablets are manufactured, for example, by filling HMBCa powder into hard capsules using a filling machine. Of course, the health food is not limited to tablets, and may be in the form of a powder, or may be dissolved in liquid to form a health drink or the like.

The HMBCa powder containing HMBCa hydrate as a main component according to the above embodiment has a spherical crystal system, an angle of repose of 35° or less (preferably 30° or less), and an apparent density of 0.5 g/ ml or more (preferably 0.54 g/ml or more) and has high fluidity. As is clear from the results of Examples described later, it is possible to compress the tablets by the direct compression method. That is, according to the HMBCa powder according to the embodiment, it is possible to provide an HMBCa powder whose fluidity has been improved to the point where it has tableting suitability for direct tableting, which requires high fluidity.

(Examples 1 to 6)
Next, an example performed to confirm the crystal system, angle of repose, and apparent density of HMBCa powder according to the embodiment will be described. Examples 1 to 6 are examples of HMBCa powders obtained by dissolving powdered HMBCa hydrate as a raw material, dissolving it in hot water, filtering it, and spray-drying it as described above. The system, angle of repose, and apparent density were confirmed. The HMBCa hydrate used as a raw material was produced using a known manufacturing method: an oxidation reaction process using diacetone alcohol and sodium hypochlorite, a purification process such as extraction and purification, a drying process using shelf drying, a pulverization process, and a sieving process. It was manufactured by obtaining Note that in Examples 1 to 3 and Examples 4 to 6, HMBCa hydrate from the same manufacturer was used as a raw material. The results of the crystal system, angle of repose, and apparent density of each of Examples 1 to 6 are shown in FIG.

Furthermore, a microscopic photograph of Example 1 is shown in FIG. 3, a microscopic photograph of Example 2 is shown in FIG. 4, and a microscopic photograph of Example 3 is shown in FIG.

(Comparative Examples 1 to 9)
On the other hand, as Comparative Examples 1 to 9, the crystal system, angle of repose, and apparent density of HMBCa powders that were not dissolved in hot water, filtered, and spray-dried as in Examples were confirmed. These were manufactured using known manufacturing methods including an oxidation reaction process using diacetone alcohol and sodium hypochlorite, a purification process such as extraction and purification, a drying process using shelf drying, a pulverization process, and a sieving process. It is something. Comparative Example 1 and Comparative Example 7 are commercially available products, and Comparative Examples 2 to 4, Comparative Examples 5 to 6, Comparative Example 8, and Comparative Example 9 are manufactured by different manufacturers, but all of them are powdered products that were used as raw materials in the examples. corresponds to HMBCa hydrate. The results of the crystal system, angle of repose, and apparent density of each of Comparative Examples 1 to 9 are also shown in FIG. Note that the crystal system was confirmed by microphotographs. The angle of repose and apparent density were measured by the measurement method described above.

Furthermore, a microscopic photograph of Comparative Example 1 is shown in FIG. 6, a microscopic photograph of Comparative Example 2 is shown in FIG. 7, and a microscopic photograph of Comparative Example 7 is shown in FIG.

As is clear from the results in FIGS. 2 to 5, it was confirmed that Examples 1 to 6 all had spherical crystal structures. Additionally, in Examples 1 to 6, it was confirmed that the average particle diameter was 100 μm or less. Furthermore, it was confirmed that the angle of repose was 35° or less and the apparent density was 0.5 g/ml or more. On the other hand, Comparative Examples 1 to 9 (including commercially available products) all had acicular crystal structures. Furthermore, the angle of repose was 45° or more, and the apparent density was 0.41 g/ml or less.

(Tablet compression test)
Furthermore, the suitability for tabletting was confirmed when direct tableting was performed using the HMBCa powders of Examples 1 to 6 and the HMBCa powders of Comparative Examples 1 to 9 as raw materials. None of the HMBCa powders of Examples 1 to 6 caused tableting problems and could be compressed by the direct compression method. On the other hand, the HMBCa powders of Comparative Examples 1 to 9 suffered from tableting problems and could not be compressed by the direct tableting method. In other words, it is not possible to use a direct tableting method, but instead a granule tableting method is used in which the tablets are made into granules and then compressed into tablets.

Although the present invention has been described in detail in accordance with specific embodiments, various substitutions, modifications, changes, etc. in form and details may be made to the present invention as defined by the claims. It will be apparent to those of ordinary skill in the art that anything may be done without departing from the spirit and scope.

Claims (1)

Dissolving HMBCa hydrate having needle-like crystals to prepare a solution containing HMBCa; spray-drying the HMBCa-containing solution to obtain HMBCa hydrate having spherical crystals ; A method for producing an HMBCa powder composition , comprising :