JP2024059141A - Method for producing eggshell membrane-containing fine powder - Google Patents

Abstract

[Problem] To provide a method for producing finely pulverized powder of eggshell membrane with improved digestive and absorptive efficiency. [Solution] By finely pulverizing an eggshell membrane-containing powder or an eggshell membrane-containing fine powder using a media stirring mill, an eggshell membrane-containing fine powder is produced that has a volume average particle size of 6 μm or less and/or a maximum volume average particle size of 20 μm or less as measured by laser diffraction method, and that has a more uniform particle size and improved digestive and absorptive efficiency compared to conventional fine powders. [Selected Figure] Figure 1

Description

The present invention relates to a method for producing eggshell membrane-containing fine powder by finely grinding eggshell membrane-containing powder.

The eggshell membrane is the membrane found inside the eggshell of avian eggs such as chicken eggs. It consists of two layers, an inner and an outer, with the outer membrane adhering closely to the inner surface of the eggshell and the inner membrane enveloping the egg white. It has antibacterial properties and protects the developing embryo from infection. The main component of the eggshell membrane is fibrous protein including types I, V and X collagen, etc. These proteins contain a lot of cysteine and have a mesh-like structure made of tough fibrous proteins. The eggshell membrane also contains glucosamine, desmosine and hyaluronic acid, and is relatively stable against acids, alkalis and proteases, and is insoluble in water.

Because eggshell membrane is composed primarily of mesh-structured fiber and is insoluble in water, it is difficult for the human body to digest and absorb. For this reason, there is a demand for improvements in digestive and absorption efficiency. For example, in order to make insoluble eggshell membrane soluble in water, a technology has been developed in which proteins are hydrolyzed with acid, alkali, or enzymes to produce hydrolyzed eggshell membrane (Patent Document 1). However, because the hydrolysis process utilizes a chemical reaction, there is a disadvantage that various active ingredients contained in the eggshell membrane are easily deteriorated, denatured, or lost during the hydrolysis process.

For this reason, mechanical treatments have been carried out to physically pulverize the eggshell membrane into finer particles to increase the surface area per unit volume of the eggshell membrane particles and improve the efficiency of dissolving and eluting the eggshell membrane components per unit time. For example, a method has been proposed in which eggshell membrane powder is pulverized in a jet mill to produce a fine powder (Patent Document 3) with a volume average particle size of 6 μm or less (Patent Document 2) to improve the efficiency of digestion and absorption of the eggshell membrane components, but even so, the digestion and absorption rate is just under 60%, which is not sufficient.

Patent No. 5179847 JP 2013-216652 A Japanese Patent Application Laid-Open No. 2-231426

Through repeated experiments in which eggshell membranes were crushed more finely, the inventors found that the digestive and absorptive efficiency of eggshell membranes does not increase simply in proportion to particle size. In other words, even if eggshell membranes are crushed to reduce the particle size to the levels shown in Patent Documents 2 and 3 or below, further improvement in digestive and absorptive efficiency cannot be expected.
The present invention has been made in consideration of the above-mentioned circumstances, and its objective is to provide an eggshell membrane-containing fine powder that has improved digestive and absorption efficiency compared to conventional powders and that has a uniform particle size, allowing the amount contained in a tablet to be increased several times, and a method for producing the same.

The inventors discovered that by grinding conventional eggshell membrane-containing fine powders in a media-agitating mill, such as a ball mill, it is possible to obtain fine powder molecules that are smaller and more uniform in size than conventional fine powders, although the overall volume average particle size does not change, and the mesh structure of the fibrous protein is loosened, resulting in a softer texture. This led to the completion of the present invention, as it was discovered that a uniformly dispersed and solubilized eggshell membrane-containing fine powder can be obtained.

The present invention relates to the following methods for producing eggshell membrane-containing fine powders (1) to (5).
(1) A method for producing a fine powder containing eggshell membrane, comprising finely pulverizing an eggshell membrane-containing powder using a media stirring mill to produce a fine powder containing eggshell membrane having a volume average particle size of 6 μm or less and/or a maximum volume particle size of 20 μm or less, as measured by a laser diffraction method.
(2) The manufacturing method described in (1) above, wherein the eggshell membrane-containing powder is an eggshell membrane-containing powder pulverized with a jet mill.
(3) The manufacturing method described in (1) above, wherein the media stirring mill is a ball mill.
(4) A method for producing an eggshell membrane-containing fine powder, comprising pulverizing an eggshell membrane-containing powder in a jet mill, and finely pulverizing the resulting powder in a media stirring mill to produce an eggshell membrane-containing fine powder having a volume average particle size of 6 μm or less and/or a volume maximum particle size of 20 μm or less as measured by a laser diffraction method.
(5) A manufacturing method described in any one of (1) to (4) above, which produces a fine powder containing eggshell membranes that contains many small, uniform powder pieces and is more easily dispersed uniformly than a finely pulverized powder produced by a jet mill.

In the case of eggshell membrane fine powder, reducing the particle size does not improve the digestive and absorption efficiency much at all. This is because only some of the fractured and crushed surfaces created during the crushing process of the eggshell membrane become more soluble in digestive fluids, while the strong mesh structure of the eggshell membrane particles themselves is maintained, so that they remain insoluble in digestive fluids.
In contrast, the eggshell membrane-containing fine powder pulverized by the media agitation mill of the present invention has improved digestive and absorptive efficiency compared to conventional eggshell membrane fine powder pulverized by a jet mill, etc. This effect of improving digestive and absorptive efficiency is not merely attributable to the smaller particle size, since the volume average particle diameters of both are comparable, but is presumably due to the destruction of the strong fibrous mesh structure inherent to the eggshell membrane in the process of pulverizing the eggshell membrane powder with the media agitation mill, loosening and softening the fibrous protein, making the eggshell membrane fine particles more easily soluble in digestive fluids as a whole.

Furthermore, when observed with a laser microscope, the fine powder ground with a jet mill contains many small pieces, but there are also many pieces with fairly large lengths along the long axis of the fragments (long pieces), resulting in a large variation in length. On the other hand, the fine powder ground with a ball mill contains many relatively small pieces with uniform long pieces, and the number of large pieces gradually decreases, and since there are many small, uniform pieces, it is thought that they are easier to disperse evenly.

Since the particle size is uniform overall, the amount of the compound in the tablet can be increased several times, making it possible to produce a product with an increased amount of the main raw material. At the same time, the amount of excipients in the tablet can be reduced, and such a change in the raw material composition allows the sugar coating layer to be made thinner, making the tablet smaller and easier for consumers to take, making it suitable for use in various forms such as food and beverages, supplements, and medicines.
The uniform particle size further improves the manufacturing stability of products containing eggshell membrane fine powder. It is much easier to mix with other ingredients, and the ethanol used during granulation penetrates evenly throughout the product, making it easier to manufacture, and the granule particles are also uniform. The uniform granules also enable stable production in the next step of tableting, and the weight and hardness are also stable.

The particle size distribution curve and measurement results by laser diffraction method for the eggshell membrane-containing fine powder milled for 12 hours using the ball mill produced in Example 2. Laser microscope photographs of the eggshell membrane-containing fine powders produced in Examples 1 and 2. The two laser microscope images in FIG. 2 were binarized using ImageJ (v.1.53c), and the maximum distance between two points (Ferret't Diameter) was measured (the length of the powder particles in the long axis direction was measured). The vertical axis shows the number of particles, and the horizontal axis shows the size of the powder particles (length in μm).

The eggshell membrane, which is the raw material for the eggshell membrane-containing fine powder of the present invention, can be any membrane found inside the eggshell of any egg of a terrestrial oviparous animal, particularly an avian egg. In particular, eggshell membrane from a chicken egg is preferred in terms of ease of availability and cost. The eggshell membrane-containing powder used in the present invention is a powder that contains at least eggshell membrane, and may be a powder made by powdering an eggshell membrane-containing raw material, such as peeled eggshell membrane, using a known blender, mixer, mill, or grinder, or may be a commercially available eggshell membrane-containing powder.

The eggshell membrane-containing powder to be pulverized in the media stirring mill to obtain the eggshell membrane-containing fine powder of the present invention is preferably one having a volume average particle size or volume maximum particle size of 40 μm or less, as this shortens the pulverization time, and is preferably one pulverized using a jet mill in which eggshell membrane-containing raw materials are caused to collide with each other in a gas, as this suppresses thermal denaturation.

Compared to conventional methods that use hard crushing elements such as rotary blades to crush raw materials, the crushing method using a jet mill generates almost no frictional heat caused by contact and collision between the crushing elements and raw materials during crushing. This causes less damage to components that are easily denatured, deteriorated, or decomposed by heat, such as amino acids and proteins contained in the eggshell membrane, and the active ingredients in the eggshell membrane are less likely to be lost during the crushing process.

In the production of the eggshell membrane-containing powder, the eggshell membrane-containing raw material is preferably pulverized by a jet mill until the volume average particle size is 40 μm or less, more preferably 20 μm or less, and even more preferably 10 μm or less. It is also preferable to pulverize until the volume maximum particle size is 20 μm or less.
If the eggshell membrane-containing powder after pulverization by the jet mill contains coarse particles having a particle size exceeding 40 μm, the coarse particles may be removed by classification using a sieve with mesh size of 40 μm or less.

In addition, before the eggshell membrane-containing powder is pulverized by the media stirring mill, the eggshell membrane-containing powder can be pulverized by a jet mill to obtain an eggshell membrane-containing fine powder having a volume average particle size of 6 μm or less and/or a volume maximum particle size of 20 μm or less, and then this can be pulverized by the media stirring mill, thereby shortening the time required for pulverization by the media stirring mill.In addition, when producing an eggshell membrane-containing powder by pulverization with a jet mill, the pulverization can be continued as is to obtain a finely pulverized product by the jet mill.

In this specification, the "volume average particle size" and "volume maximum particle size" of the eggshell membrane-containing powder or fine powder refer to values measured using a laser diffraction particle size distribution measuring device. When measuring particle size, a measurement sample is used in which fine powder or the like is dispersed in water using a surfactant. In addition, "volume average particle size" refers to the particle size at which the cumulative volume from the small particle size side in the volume-based particle size distribution is 50%.

A media agitation mill is a grinding machine that grinds and disperses raw materials by putting them into a container filled with media and agitating them together using a stirring device. When the media is given motion by agitation, shear and frictional forces are generated and grinding and dispersion are carried out. There are various types of media, such as "balls," "pebbles," and "beads." When the grinding operation is carried out in gas, it is called "dry grinding," and when it is carried out in liquid, it is called "wet grinding."

Dry bead mills and ball mills (rolling type, vibrating type, etc.) are commonly used as dry fine grinding machines. Beads are media with a diameter of 2 mm or less, and balls are media with a diameter of 10 to 50 mm. Bead mills have extremely strong energy, 100 to 500 times stronger than ball mills, and ball mills are preferred for finely grinding eggshell membrane-containing powders.

The eggshell membrane-containing powder or eggshell membrane-containing fine powder is pulverized in a ball mill until the volume average particle size is 6 μm or the volume maximum particle size is 20 μm or less. The time required for pulverization varies depending on the type of ball mill and the size of the eggshell membrane-containing powder, but for example, it is 1 to 12 hours using a ball mill (BM-100, manufactured by Oshima Iron Works Co., Ltd.). The "volume average particle size" and "volume maximum particle size" are measured at any time using a laser diffraction particle size distribution analyzer (LMS-30, manufactured by Seishin Co., Ltd.).

The fine powder containing eggshell membranes thus pulverized can be used to manufacture oral tablets, granules, capsules, or drinks; various foods and beverages, supplements, or medicines; liquids, emulsions, and creams to be applied to the skin for the purposes of disease prevention, treatment, beauty, etc.; and liquids, emulsions, and creams to be applied to hair, eyebrows, eyelashes, etc., such as mascara and treatment liquids.

The eggshell membrane-containing fine powder produced by the stirring media mill has a uniform and small particle size overall, which improves digestive and absorption efficiency compared to conventional eggshell membrane fine powder. Not only has the quality been improved, but the amount of main ingredient in the tablet can be increased while the amount of excipient can be reduced, resulting in a thinner sugar coating layer and smaller tablets that are easier to swallow.
Furthermore, in the production of pharmaceutical preparations, the powder can be easily mixed with other compounded raw materials, the granule particles are uniform, making tableting stable, and products containing eggshell membrane-containing fine powder with stable weight and hardness can be produced.

The amount of eggshell membrane-containing fine powder contained in the oral composition is not particularly limited, but from the viewpoints of smooth granulation and tableting and increasing the effect of the eggshell membrane component when the tablet is orally taken, it is preferable that the eggshell membrane component is contained in a proportion of 10 to 90% by mass, and more preferably 30 to 80% by mass, of the total mass of the oral composition.

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[Example 1]
[Production of eggshell membrane-containing fine powder (part 1)]
The eggshell membrane-containing powder used as the raw material was product name "EM Powder 300" (manufactured by Kewpie Corporation).
A single track jet mill (FS-4, manufactured by Seishin Co., Ltd.) was used as the jet mill, and fine pulverization was carried out at an air volume of 1.2 ^m3 /min and power of 11 kW until the volume maximum particle size was about 800 mesh (approximately 20 μm in mesh size). When the particle size after pulverization was measured using a laser diffraction particle size distribution measuring device (LMS-30, manufactured by Seishin Co., Ltd.), the volume maximum particle size was 19.6 μm and the volume average particle size was 5.8 μm (hereinafter referred to as "800 mesh fine powder").

[Example 2]
[Production of eggshell membrane-containing fine powder (part 2)]
The eggshell membrane-containing fine powder produced in Example 1 was used as the raw material eggshell membrane-containing fine powder.
The eggshell membrane-containing fine powder was finely pulverized for 12 hours using a ball mill (BM-100, manufactured by Oshima Iron Works Co., Ltd.). The particle size after pulverization was measured using a laser diffraction particle size distribution measuring device (LMS-30, manufactured by Seishin Co., Ltd.), and the maximum volume particle size was 10 μm and the volume average particle size was 3.6 μm (hereinafter referred to as "ball milled fine powder").
The measured particle size distribution curve and the measurement results are shown in FIG.

Figure 2 shows laser microscope photographs of the eggshell membrane-containing fine powders produced in Examples 1 and 2. It can be seen that the ball mill fine powder on the left (in 0.5% pure water) has smaller, more uniform particles than the 800 mesh fine powder on the right (in 1.0% pure water), and is easier to disperse uniformly.
This is also shown in Figure 3, which shows the particle size distribution obtained by binarizing the two laser microscope images in Figure 2 using ImageJ (v.1.53c) and measuring the maximum distance between two points (Ferret's Diameter) (the length in the major axis direction of the powder particles).

The vertical axis of Figure 3 is the number of particles, and the horizontal axis is the size (μm) of the powder particles, showing the number of particles with sizes of 2-4 μm, 4-6 μm, .... The size of the powder particles is the length in the major axis direction measured from the image.
The ball milled fine powder has many relatively small pieces evenly distributed across a small size range, whereas the 800 mesh fine powder has many small pieces but also very large pieces. Thus, the ball milled fine powder has small, uniform powder particles with a uniform particle size.

The present invention relates to the following methods for producing eggshell membrane-containing fine powders (1) to ( 4 ).
( 1 ) A method for producing an eggshell membrane-containing fine powder, comprising: pulverizing an eggshell membrane-containing fine powder pulverized in a jet mill ; dry- pulverizing the eggshell membrane-containing fine powder in a media stirring mill; and producing an eggshell membrane-containing fine powder having a volume average particle size of 6 μm or less and/or a maximum volume particle size of 20 μm or less, as determined by a laser diffraction method.
( 2 ) The manufacturing method according to (1) above, wherein the media stirring mill is a ball mill.
( 3 ) The manufacturing method described in (1) above , wherein the eggshell membrane-containing fine powder pulverized by the jet mill is an eggshell membrane-containing fine powder having a volume average particle size of 6 μm or less and/or a volume maximum particle size of 20 μm or less , as measured by a laser diffraction method.
( 4 ) A manufacturing method according to any one of (1) to ( 3 ) above, which produces a fine powder containing eggshell membranes that has a larger number of small, uniform powder pieces and is more easily dispersed uniformly than a finely pulverized powder produced by a jet mill.

Claims (5)

A method for producing eggshell membrane-containing fine powder, comprising pulverizing eggshell membrane-containing powder with a media stirring mill to produce eggshell membrane-containing fine powder having a volume average particle size of 6 μm or less and/or a volume maximum particle size of 20 μm or less as measured by laser diffraction. The method according to claim 1, wherein the eggshell membrane-containing powder is an eggshell membrane-containing powder pulverized with a jet mill. The manufacturing method according to claim 1, wherein the media-agitated mill is a ball mill. A method for producing eggshell membrane-containing fine powder, in which eggshell membrane-containing powder is pulverized in a jet mill, and the resulting powder is pulverized in a media stirring mill to produce eggshell membrane-containing fine powder having a volume average particle size of 6 μm or less and/or a volume maximum particle size of 20 μm or less as measured by laser diffraction. The method according to any one of claims 1 to 4, which produces a fine powder containing eggshell membranes which has a larger number of small, uniform powder pieces and is more easily dispersed uniformly than a finely pulverized powder produced by a jet mill.