JP7587870B2 - Use of α-cyclodextrin - Google Patents

Description

In view of the extremely low solubility of cyclodextrin, a substance having various uses, particularly β-cyclodextrin, in water at low temperatures mainly below room temperature, the present invention provides a technology capable of improving or enhancing the solubility of β-cyclodextrin. More specifically, the present invention relates to a technology capable of improving the solubility of β-cyclodextrin by, for example, mixing α-cyclodextrin with β-cyclodextrin.
In addition, in view of the fact that oligosaccharides, which are also substances having various uses, and in particular lactose fructose oligosaccharides, fructooligosaccharides, galactooligosaccharides, and isomaltooligosaccharides, are hygroscopic, the present invention also provides a technique for improving or enhancing the hygroscopicity of these oligosaccharides. More specifically, the present invention relates to a technique for improving the hygroscopicity of oligosaccharides by, for example, mixing α-cyclodextrin with these oligosaccharides.

Cyclodextrin (hereinafter sometimes referred to as cyclodextrin, CD, or cyclic oligosaccharide) is a type of oligosaccharide in which glucose residues are cyclically bonded via α-1,4-bonds. Known examples include α-cyclodextrin, which consists of six glucose residues, β-cyclodextrin, which consists of seven glucose residues, and γ-cyclodextrin, which consists of eight glucose residues.
Oligosaccharides are formed by binding several monosaccharides such as glucose and fructose via glycosidic bonds, and have a molecular weight of about 300 to 1600. There are various types of oligosaccharides, including disaccharides such as sucrose, lactose, trehalose, maltose, and isomaltose, trisaccharides such as lactosucrose, raffinose, maltotriose, and 1-kestose, and tetrasaccharides such as stachyose and nystose.

Cyclodextrin has various applications, such as stabilization of unstable substances, stabilization of volatile substances, masking of odors, solubilization of poorly soluble and insoluble substances, etc. In other words, it is widely used in pharmaceutical applications, food applications, etc.
Oligosaccharides also have a variety of uses. In particular, resistant oligosaccharides, which cannot be digested or absorbed, are known to increase beneficial intestinal bacteria such as bifidobacteria and improve the intestinal flora. They are therefore used in health foods and other products in the hope that they will have various physiologically active effects.

Here, β-cyclodextrin in particular has a property of having very low solubility in water, making it difficult to meet the above-mentioned applications. Specifically, for example, the solubility in water at 25°C and 100 mL is about 14.5 g for α-CD, 1.8 g for β-CD, and 23.2 g for γ-CD.
In addition, oligosaccharides such as lactose fructose oligosaccharides, fructooligosaccharides, galactooligosaccharides, and isomaltooligosaccharides have high hygroscopicity and are difficult to use and distribute while maintaining their powdery properties. Therefore, the applications of these oligosaccharides in a powdered state are limited, and the above-mentioned usefulness is not fully utilized.

Therefore, β-cyclodextrin, which has low solubility, must be prepared in a dilute solution and cannot be used in high concentrations when blended, and the solubility must be increased by mixing it with sugars such as monosaccharides or low molecular weight oligosaccharides, chemically modifying it, or adding sugars such as maltose. Specifically, there are mixtures with sugars, modified CDs such as hydroxypropyl groups, and branched CDs such as maltosyl groups. In addition, examples of technologies for improving solubility include Patent Document 1 (JP Patent Publication 8-508711).
Oligosaccharides are highly hygroscopic, and as oligosaccharide powder absorbs moisture over time, turning into a candy-like substance. Therefore, there has been a long awaited development of a material and mixing method that can be mixed with oligosaccharides to reduce moisture absorption and maintain their powdered state.

Special Publication No. 8-508711

Under these circumstances, if the solubility of highly useful cyclodextrin in water could be improved, it would be possible to prepare a concentrated solution and also to use it at a high concentration when blended with other substances, thereby enabling it to be used more effectively and efficiently.
Furthermore, if the hygroscopicity of highly useful oligosaccharides could be improved, it would be possible to produce them in bulk or other powder form, allowing them to be used more effectively.

Furthermore, as described above, since cyclodextrin is expected to be used for pharmaceutical purposes, food purposes, and the like, it is desirable to avoid chemical modification, chemical treatment, and the like as much as possible.
The same is true for oligosaccharides.

Under these technical circumstances, a technology that can improve the solubility of cyclodextrin without the above-mentioned modifications or additions has been eagerly awaited. If this problem could be solved, the range of uses for cyclodextrin, which is a useful substance, would be greatly expanded, and its effects on the human body would be minimized. It is also believed that this would reduce manufacturing costs and pave the way for mass production. This is expected to be a major technological contribution.
If the hygroscopicity of oligosaccharides can be improved without chemical treatment or the like, a similar contribution can be expected.

In order to solve the above problems, the present inventors have intensively investigated substances, methods, conditions, etc. that can satisfy the above conditions. As a result, they have unexpectedly found that there exists a substance that satisfies the conditions when closely related substances are mixed together. In other words, they have found that by mixing α-cyclodextrin with β-cyclodextrin, the solubility of β-cyclodextrin can be increased without the above-mentioned modification or addition, and have completed the present invention.
As for oligosaccharides, the inventors of the present application have also investigated materials and mixing methods that can suppress moisture absorption and maintain a powdered state by mixing them together, and have found that mixing α-cyclodextrin with oligosaccharides such as lactosucrose (hereinafter sometimes referred to as "LS") can improve the moisture absorption of the oligosaccharides.
Therefore, it can be said that the present invention as a whole relates to the properties of α-cyclodextrin and methods for using it.

That is, the embodiments of the present invention are as follows.
(1) A method for enhancing the solubility of β-cyclodextrin in water, which comprises using α-cyclodextrin.
(2) A method of increasing the solubility of β-cyclodextrin in water by mixing α-cyclodextrin with β-cyclodextrin.
(3) A method for increasing the solubility of β-cyclodextrin in water by mixing α-cyclodextrin with β-cyclodextrin to produce a composition.
(4) A method of increasing the solubility of β-cyclodextrin in water by mixing 10% to 60% of β-cyclodextrin and 40% to 77% of α-cyclodextrin.
(5) A method for increasing the solubility of β-cyclodextrin in water by producing a composition by mixing 10% to 60% of β-cyclodextrin and 40% to 77% of α-cyclodextrin.
(6) The method according to any one of (1) to (5), further comprising adjusting Bx. to 40 to 55.
(7) A method for producing a composition which increases the solubility of β-cyclodextrin in water, comprising mixing and dissolving 60 to 90%, preferably 70 to 80%, and particularly preferably 77% α-cyclodextrin and 10 to 40%, preferably 20 to 30%, and particularly preferably 23% β-cyclodextrin, followed by filtering and spray drying.
(8) An agent for enhancing the solubility of β-cyclodextrin in water, comprising α-cyclodextrin as an active ingredient.
(9) A method for improving the hygroscopicity of oligosaccharides, comprising using α-cyclodextrin.
(10) A method for improving the hygroscopicity of an oligosaccharide by mixing the oligosaccharide with α-cyclodextrin.
(11) A method for improving the hygroscopicity of an oligosaccharide by mixing an α-cyclodextrin with the oligosaccharide to produce a composition.
(12) A method for improving the hygroscopicity of oligosaccharides by mixing α-cyclodextrin with oligosaccharides in a ratio of 50% or more, preferably 60 to 70%.
(13) The method according to any one of (9) to (12), further comprising the steps of dissolving and drying the mixture after mixing.
(14) A method for improving the hygroscopicity of oligosaccharides by producing a composition by mixing oligosaccharides with α-cyclodextrin in a ratio of 50% or more, preferably 60 to 70%,.
(15) The method according to any one of (9) to (14), further comprising adjusting Bx to 30 to Bx 50.
(16) A method for producing a composition for improving the hygroscopicity of oligosaccharides, comprising mixing α-cyclodextrin with oligosaccharides in a ratio of 50% or more, preferably 60 to 70%, dissolving the mixture, and then drying the mixture.
(17) An agent for improving the hygroscopicity of oligosaccharides, comprising α-cyclodextrin as an active ingredient.
(18) The method according to any one of (9) to (16), characterized in that the oligosaccharide is one or more selected from lactosucrose, fructooligosaccharides, and galactooligosaccharides.
(19) The agent according to (18), characterized in that the oligosaccharide is one or more selected from lactosucrose, fructooligosaccharides, and galactooligosaccharides.
(20) An agent for increasing the solubility of β-cyclodextrin in water and improving the hygroscopicity of oligosaccharides, characterized by containing α-cyclodextrin as an active ingredient.

According to the present invention, the solubility of β-cyclodextrin in water can be easily and effectively increased. In the past, solubility was increased by chemically modifying β-cyclodextrin or by adding sugars such as maltose, but according to the present invention, it is possible to increase the solubility of β-cyclodextrin in water without the need for such modification or addition.
Furthermore, according to the present invention, the hygroscopicity of oligosaccharides, particularly lactosucrose, fructooligosaccharides, and galactooligosaccharides, can be improved simply and effectively.

Therefore, in the past, β-cyclodextrin was prepared in a dilute solution and could not be blended at a high concentration. However, according to the present invention, it is possible to prepare a concentrated solution in advance and also to blend it at a high concentration.
This has the effect of making it possible to meet the strong demand for β-cyclodextrin as described above.
In addition, the present technology makes it possible to produce the oligosaccharides in bulk or other powder form, which was previously difficult due to their high hygroscopicity. This has the effect of meeting the strong demand for oligosaccharides, particularly by making it possible to provide products in powder form.

Therefore, the present invention increases the solubility of β-cyclodextrin, which can be used for various purposes in the food, pharmaceutical, and other industries, and enables the preparation of a high-concentration, concentrated solution, thereby enabling further expansion of the uses of the substance, reduction in production costs, etc., and providing new methods of use by being able to use the substance at a high concentration, etc. In other words, the present invention is of great value both technically and economically.
In addition, oligosaccharides are also useful in various fields as described above, but it is no longer necessary to distribute them in a liquid form as in the past. If they are in a powder form, they are easy to handle and transportation costs can be reduced. They are also easy to store, which opens the way to maintaining quality for a long period of time. In this respect, the technical value of the present invention is also high.

1 is a drawing substitute photograph taken in a test tube immediately after heating and stirring of Blends 1 to 5 in Example 1. Blends 1, 2, 3, 4, and 5 are shown in the test tubes from the left. 1 is a drawing substitute photograph taken in a test tube immediately after heating and stirring of Blends 6 to 8 in Example 1. Blends 6, 7, and 8 are shown in the test tubes from the left. 1 is a drawing substitute photograph taken in a test tube immediately after heating and stirring of Blends 9 to 11 in Example 1. Blends 9, 10, and 11 are shown in the test tubes from the left. 1 is a drawing substitute photograph taken in a test tube to show the dissolved state of each of the blends 1 to 5 in Example 1 after heating and stirring, and then leaving them at room temperature for 1 hour. The test tubes on the left show blends 1, 2, 3, 4, and 5, respectively. 1 is a drawing substitute photograph of the dissolved state of the mixtures 6 to 8 in Example 1 after heating and stirring, and then leaving them at room temperature for 1 hour in test tubes. The test tubes on the left show mixtures 6, 7, and 8, respectively. 1 is a drawing substitute photograph taken in a test tube to show the dissolved state of each of the blends 9 to 11 in Example 1 after heating and stirring, and then leaving them at room temperature for 1 hour. The test tubes on the left show blends 9, 10, and 11, respectively. A. In Example 2, this is a drawing substitute photograph showing the state of dissolution immediately after adding water (25°C) and mixing and dissolving with a vortex. The three test tubes on the left are for K-100, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes in the middle are for Prototype 1, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes on the right are for α-CD, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. Photographs substituting for drawings showing the dissolution state of Example 2 (i.e., above (a)) after leaving it for about 30 minutes. The three test tubes on the left are for K-100, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes in the middle are for Prototype 1, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes on the right are for α-CD, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. Photographs substituting for drawings showing the dissolution state of C in Example 2, i.e., the above A, after being left for about 3 hours. The three test tubes on the left are for K-100, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes in the middle are for Prototype 1, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes on the right are for α-CD, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. 6 is a drawing substitute photograph showing the dissolved state of D in Example 2, that is, the above C, immediately after heating and dissolving. The three test tubes on the left are K-100, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes in the middle are Prototype 1, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes on the right are α-CD, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. Photographs substituting for drawings showing the dissolution state of Example 2, i.e., the above-mentioned d, after being left at room temperature for 2 hours. The three test tubes on the left are for K-100, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes in the middle are for Prototype 1, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes on the right are for α-CD, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. Photographs substituting for drawings showing the dissolution state of the compound in Example 2, i.e., the compound in Example 2, after being left at room temperature for 20 hours. The three test tubes on the left are for K-100, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes in the middle are for Prototype 1, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. The three test tubes on the right are for α-CD, and from the left, they are prepared with Bx. 30, Bx. 40, and Bx. 50, respectively. 1 is a photograph showing the state immediately after dissolving in water (25°C) in Example 3. The test tube on the left is for Prototype 1 in Example 2, and the test tube on the right is for a simple powder mixture of α-CD and β-CD in a ratio of 77:23. 13 shows the state of the sample after being left in room temperature water overnight from the state shown in FIG. 13 in Example 3. The test tube on the left is Prototype 1 in Example 2, and the test tube on the right is a simple powder mixture of α-CD and β-CD in a ratio of 77:23. 10 is a photograph showing the state immediately after heating and dissolving in Example 3. The test tube on the left is Prototype 1 in Example 2, and the test tube on the right is a simple powder mixture of α-CD and β-CD in a ratio of 77:23. 15 shows the state of the mixture after 3 days of heating and dissolving in Example 3. The left test tube is Prototype 1 in Example 2, and the right test tube is a simple powder mixture of α-CD and β-CD in a ratio of 77:23. 11 is a photograph showing the state of the powder mixture after 48 hours in Example 5. From the left, the powder mixtures with α-CD ratios of 70%, 65%, and 60% are shown. 13 is a drawing substitute photograph showing the state of the powder mixture after 48 hours in Example 5. From the left, the powder mixtures with α-CD ratios of 55% and 50% are shown. 11 is a drawing-substitute photograph showing the state of the freeze-dried products after 48 hours in Example 5. From the left, the mixture ratios of α-CD are 70%, 65%, and 60%. Similarly, these are photographs substituting drawings showing the state of the freeze-dried products after 48 hours in Example 5. From the left, the photographs show the mixture ratios of α-CD of 55% and 50%. 1 is a micrograph (a photograph substituting a drawing) of the pulverized LS freeze-dried product of Example 7. 22 is a micrograph (a drawing substitute photograph) of the product of Example 7 shown in FIG. 21 after being left in a natural atmosphere at room temperature for one hour. FIG. 1 is a micrograph (a drawing substitute photograph) of a solution of LS-55P (the composition of which will be described later) and 50% α-CD in Example 7, which was then freeze-dried. 24 is a micrograph (a drawing substitute photograph) of the product of Example 7 shown in FIG. 23 left at room temperature in an atmosphere of natural occurrence for one week. This is a photograph showing the state after 48 hours regarding the moisture absorption prevention effect of various oligosaccharides by α-CD in Example 8. The vertical axis shows, from the top, LS, fructooligosaccharide, galactooligosaccharide, and isomaltooligosaccharide. The horizontal axis shows, from the left, the samples containing 50%, 60%, and 70% α-CD.

The present invention is described in detail below.

The present invention is characterized in that α-cyclodextrin is used to increase the solubility of β-cyclodextrin in water.

Cyclodextrin is a unique carbohydrate that is a non-reducing oligosaccharide consisting of 6 to 8 glucose units linked together in a ring, has a cavity within the molecule, and is hydrophilic on the outside and lipophilic on the inside.
In particular, it is characterized by its clathrate property (the ability to enclose various molecules within its cavity), and this property is utilized in a variety of applications for the purpose of stabilizing or improving quality.
Cyclodextrin is also becoming more and more popular in a variety of fields, including not only food, but also pharmaceuticals, cosmetics, and industrial products such as textiles and paints, and its applications are beginning to emerge.

Cyclodextrin can be produced by reacting starch with an enzyme (a CD-forming enzyme, such as glucanotransferase produced by Bacillus macerans) to form a cyclic bond of glucose through a transfer reaction of the enzyme.
A CD with six glucose molecules bound is α-CD, a CD with seven glucose molecules bound is β-CD, and a CD with eight glucose molecules bound is γ-CD.
These α-CD, β-CD, and γ-CD, including high purity ones, are commercially available from Ensuiko Sugar Refining Co., Ltd., and are therefore readily available.

The present invention is characterized in that α-cyclodextrin is used instead of the β-cyclodextrin, but it does not matter how these cyclodextrins are produced.

In the present invention, the essence is to use α-cyclodextrin in place of β-cyclodextrin, but the basic embodiment is to mix β-cyclodextrin and α-cyclodextrin. For example, a powder mixture of the two, a solution obtained by dissolving the mixture in water, or a dried product obtained by drying the mixture can be used. The blending ratio can be determined within the scope of the technical concept of the present invention, and examples of the blending ratio include 15 to 80%, preferably 20 to 60%, of β-cyclodextrin relative to the total amount of β-cyclodextrin and α-cyclodextrin. Specific examples include β-cyclodextrin:α-cyclodextrin ratios of 23:77, 40:60, 40:40, and 48:32. In this case, it is possible to simply mix β-CD and α-CD in the above ratio to increase the solubility of β-CD, or it is possible to make a composition containing β-CD and α-CD in the above ratio and mixing with other excipients. If desired, β-CD and α-CD may be used separately without being mixed. Of course, any combination ratio in which the total exceeds 100 is excluded from the scope of the present invention. The total will be determined appropriately within the knowledge of a person skilled in the art so that the total does not exceed 100 while still achieving the effects of the invention.

When the composition is prepared as described above, in addition to the active ingredients α-CD and β-CD, it is possible to contain various additives recognized in the food industry. For example, additives such as other sugars, various extracts, excipients, etc. can be added or blended. Examples of additives include the following. For example, wasabi, menthol, terpenes and other flavorings, spices, essential oils, coenzyme Q10, α-lipoic acid, vitamins, unsaturated fatty acids, lycopene, rutin, royal jelly, hesperidin, crocetin, ferulic acid, anthocyanins, catechins, isoflavones, glutathione, tea extract, citrus fruit extract, egg white, turmeric (curcumin), naringin, raspberry ketone, tocopherol, propolis, carnitine, xanthohumol, zedoary, ginseng, lingzhi, ginkgo biloba, resveratrol, etc. The types and amounts of these can be appropriately determined based on the knowledge of a person skilled in the art within the scope of the technical concept of the present invention.

When β-CD and α-CD are mixed to prepare a solution as described above, the Bx. can also be determined and prepared. According to the present invention, Bx. can be set to about 40, 50, or 55. In general, Bx. can be set to about 30 to 65, for example, about 30, 40, 50, 55, 60, or 30 to 65. Bx. is an abbreviation for Brix, which represents the amount of water-soluble solids such as sugars as a percentage. In this way, a liquid product can also be made.

Furthermore, α-CD and β-CD can be mixed and dissolved, then spray-dried to obtain a powder. This makes it possible to increase the content ratio of β-CD and to increase the Bx. A mixed solution of α-CD and β-CD with a Bx. of 30 to 65, preferably 50 to 60, is heated to 50°C or higher to completely dissolve the mixture, and then spray-dried in a spray dryer to obtain a powder.

Next, the present invention includes a technology that mixes oligosaccharides with α-CD, suppresses their hygroscopicity, and allows them to be maintained in a powder state. In other words, the present invention can be said to share a common technical field and technical feature in that it is an invention that utilizes the properties of α-CD as a whole.

Oligosaccharides are sugars formed by the glycosidic bonds of several monosaccharides such as glucose and fructose, and have a molecular weight of about 300 to 1600. Some oligosaccharides increase the number of beneficial bacteria in the intestines, meaning that they are not digested in the body and reach the large intestine to become a source of assimilation for beneficial bacteria, some oligosaccharides do not increase blood sugar levels, and some are low in calories, and they play a central role in prebiotics.

Types of oligosaccharides include the above-mentioned lactosucrose (LS), fructooligosaccharides, galactooligosaccharides, and isomaltooligosaccharides. Lactosucrose can be produced by an enzymatic reaction between lactose and sucrose, and has the characteristic of exhibiting the same sweetness and physical properties as sucrose. Fructooligosaccharides are found in onions and garlic, and have a mild sweetness. Galactooligosaccharides are found in breast milk and cow's milk, and can also be produced by an enzymatic reaction of lactose. Isomaltooligosaccharides are oligosaccharides whose main component is glucose.

Fructooligosaccharides are also believed to be effective in preventing tooth decay and promoting calcium absorption, as they are less likely to cause tooth decay. Galactooligosaccharides are believed to increase bifidobacteria in the human intestine. LS also aids in calcium absorption and strengthens bones. In this way, it has become clear that oligosaccharides have extremely significant health supplement effects.

The basic technical idea of the present invention is to improve the hygroscopicity of oligosaccharides by applying α-CD to oligosaccharides having such effectiveness. In the embodiment, the basic idea is to mix α-CD with oligosaccharides. The mixing ratio can be determined within the range in which the effects of the present invention are achieved, but it is preferable for the α-CD content to be 60% or more. It can also be preferably 65% or more, and more preferably 70% or more. Specifically, the solid content ratio of oligosaccharides to α-CD can be 40:60, 30:70, etc.

As stated above, the present invention can simply mix oligosaccharides and α-CD in the above ratio, or can mix with other excipients recognized in the industry. Also, as stated above, cases where the overall mixing ratio exceeds 100 are excluded, and the composition can be used.

Furthermore, in the present invention, oligosaccharides and α-CD can be mixed, dissolved, and then freeze-dried. The Bx. during dissolution can also be adjusted (Bx. 25 to 65), for example, to about Bx. 30.

As a drying method, in addition to freeze drying, any method used by a person skilled in the art that can achieve the effects of the present invention, such as spray drying, can be used. Spray drying can be performed even with a higher Bx of about 50. The composition may also be granulated.

The following describes examples of the present invention, but the present invention is not limited to these examples, and various modifications are possible within the technical concept of the present invention.

<Combination test of mixtures containing a large amount of β-CD>
In order to improve the solubility of β-CD in water, the formulation of a mixture containing a large amount of β-CD was investigated.

Mixtures containing a large amount of β-CD (compounds 1 to 11) were prepared in the proportions shown in Table 1 below.

The preparation method is as follows: 1) α-CD or dextrins A and B were placed in a test tube and water was added. 2) The test tube was placed in boiling water and α-CD or dextrins A and B were completely dissolved. 3) β-CD was added and mixed in a vortex, then heated for a while in a boiling water bath and mixed again in a vortex. Dextrins A and B were Sandec #FN70 and Sandec #100 manufactured by Sanwa Denpuku Kogyo Co., Ltd.

The results are shown in Figures 1 to 3 and Figures 4 to 6. First, Figures 1 to 3 show the state of dissolution of each formulation immediately after heating and stirring. Immediately after heating and stirring, β-CD was dissolved in formulations 1, 2, 6, 7, and 9. From these results, it was thought that α-CD was most suitable as a mixture, followed by dextrin A and dextrin B in that order.

Next, after heating and stirring each of the above formulations, they were left at room temperature for 1 hour, and the solubility of the substances in the test tubes was observed. The results are shown in Figures 4 to 6. The results were as follows:
That is, even after being left at room temperature for 1 hour, the compounds 1, 2, and 6 were dissolved. Dextrins A and B formed large amounts of precipitates.

<Comparative test of solubility in water with commercially available products>
The solubility of Prototype 1 (the present invention, composition is as follows: α-CD:β-CD=77:23) in water was compared with that of commercial products K-100 and α-100 (both manufactured by Ensui-ko Sugar Refining Co., Ltd.).

The mixing ratio and method of Prototype 1, K-100, and α-100 are as shown in Table 2 below.

The preparation method is as follows: 1) Various CDs and water (25°C) were placed in a test tube and mixed and dissolved using a vortex (Bx. was prepared at 30, 40, and 50). 2) The above test tube was placed in boiling water and heated, and the various CDs were completely mixed and dissolved using a vortex.

The results are shown in Figure 7. This shows the state immediately after adding water (25°C) and mixing and dissolving using a vortex. When mixed with room temperature water, prototype 1 and K-100 appeared to dissolve, but α-100 did not. Also, prototype 1 seemed to dissolve more easily than K-100.

The results are shown in Figure 8. This is the state of B, i.e., the above A, after it had been left for about 30 minutes. When the above A was left at room temperature for about 30 minutes, the air bubbles escaped from K-100 and it became clear, but fine crystals began to precipitate in Prototype 1. This is likely β-CD.

The results are shown in Figure 9. This is the state of C, i.e., the above A, after it had been left for approximately 3 hours. When the above A was left at room temperature for approximately 3 hours, a crystalline precipitate that appeared to be β-CD was formed in prototype 1. The amount of precipitate three hours after dissolving at room temperature was greatest in α-100, followed by prototype 1 and then K-100.

The results are shown in Figure 10. This is the state immediately after heating and dissolving D, i.e., the above C. Both prototype 1 and K-100 easily became clear solutions when heated. α-100 also dissolved when heated, but it took time for the Bx. 40 and Bx. 50 solutions to dissolve.

The results are shown in Figure 11. This is the state of E, i.e., the above D, after being left at room temperature for 2 hours. After being completely dissolved by heating and left at room temperature for 2 hours, the K-100 solution became whitish and cloudy, but no precipitation was observed in the Bx.50 solution.
The α-100 solution also turned whitish, and slight α-CD crystal precipitates were formed in the Bx.40 solution, and many in the Bx.50 solution.
On the other hand, in the case of Prototype 1, the solution remained transparent, but in the Bx.50 solution, a small amount of crystalline precipitate thought to be β-CD was formed.

The results are shown in Figure 12. This is the state of (F), i.e., (D) above, after standing at room temperature for 20 hours. After being completely dissolved by heating and left at room temperature for 20 hours, a slight crystal precipitation of α-CD was confirmed even in the Bx. 30 solution of α-100.
In the case of K-100, a white hazy substance was precipitated, suggesting the possibility that a high molecular weight sugar was precipitated. In addition, a crystalline precipitate was also confirmed in the solution of Bx. 50.
For Prototype 1, a large amount of crystalline precipitate was observed in the Bx. 50 solution, and a slight amount in the Bx. 40 solution, but the Bx. 30 solution was a transparent solution with no precipitate.

<Comparative test of solubility between the above prototype 1 and a powder mixture>
A comparison test was carried out on the solubility (Bx.30) of Prototype 1 in Example 2 above and a powder obtained by mixing α-CD and β-CD in a powder ratio of 77:23.

The results are shown in Figure 13. A large difference in solubility was observed in room temperature water between the powder obtained by mixing and dissolving α-CD and β-CD and spray drying (Prototype 1 in Example 2 above) and the powder obtained by simply mixing α-CD and β-CD in powder form. The powder mixture was also effective, but the solubility of Prototype 1 was overwhelmingly better.
When dissolved in water at room temperature and then left to stand overnight (Figure 14), prototype 1 also produced a precipitate, but the amount was less than that of the powder mixture.
On the other hand, when heated and dissolved, all the compositions were completely dissolved (FIG. 15), and even after 3 days, no precipitation or the like occurred, but the powder mixture turned into a slightly whitish solution (FIG. 15).

The findings from the above examples can be roughly summarized as follows. That is, when Prototype 1 in Example 2 was dissolved in water at room temperature, it initially seemed to dissolve more easily than K-100, but when left as is, it produced more precipitate than K-100.

When dissolved by heating, prototype 1 was a clearer liquid than K-100 even after time had passed, and among the examples, only the Bx. 30 solution of prototype 1 was a clear liquid that did not produce any precipitate even 20 hours after dissolution by heating.

The amounts of precipitates after 20 hours of heating and dissolving were as follows:
α-CD (Bx.50) > α-CD (Bx.40) > Prototype 1 (Bx.50) > K-100 (Bx.50) > K-100 (Bx.40) > K-100 (Bx.30) = Prototype 1 (Bx.40) > Prototype 1 (Bx.30).

In addition, when the solubility of prototype 1 was compared with that of a powder mixture of α-CD and β-CD in the same ratio as prototype 1, the solubility in room temperature water was clearly different, with prototype 1 being easier to dissolve (Example 3, etc.).

Generally, CD is not thought of as being used in a high concentration state, but Prototype 1 maintained a clear solution state even at Bx. 30 when dissolved by heating.

Even if the blend ratio and Bx. are different, the solubility of β-CD is thought to be higher than that of the prior art, and a significant effect is thought to be achieved.

<Comparative test of the moisture absorption prevention effect of CD and dextrin on LS>
Next, a test was conducted to verify the extent to which the hygroscopicity of LS was improved by mixing it with CD and dextrin.

(Method) LS-55P (LS 55% or more, sucrose 10% or less, lactose 25% or less), dextrin, α-, β-, and γ-CD were mixed in arbitrary ratios, dissolved in Bx. 30, and then freeze-dried. β-CD did not completely dissolve and a precipitate formed, but it was mixed well after freeze-drying. 5 g of each was placed in a weighing dish (made of plastic) and left to stand in a room with a humidity of 62% to 76%, and the weight change and changes in state caused by moisture absorption were observed.

(Results) The results are shown in Table 3. When stored for 24 hours under high humidity conditions, dextrin also showed a moisture absorption suppression effect at a mixing ratio of 70%, and although it only partially dissolved, its effect was clearly less than that of CD. In comparison, α-CD showed no dissolution and remained solid at a mixing ratio of 60% or more, demonstrating excellent moisture absorption suppression, and although solidification was observed at a mixing ratio of 60% or more, it was still dissolvable.

<α-CD and LS mixing methods and mixing ratio comparison test>
A test was carried out to verify the extent to which the hygroscopicity of LS and α-CD could be improved by changing the mixing method and mixing ratio of LS and α-CD.

(Method) LS-55P and α-CD were mixed in powder form at an arbitrary ratio, and then dissolved in Bx. 30 and freeze-dried. 5 g of each was placed in a weighing dish (made of plastic) and left to stand in a room with a humidity of 50% to 61%. The weight change and changes in state caused by moisture absorption were observed.

(Results) The results are shown in Tables 4 and 5. Table 4 is for the powder-powder mixture, and Table 5 is for the freeze-dried product. In the powder-powder mixture, when the ratio of α-CD was 55% or less, dissolution was observed after 24 hours, and when it was 60% or more, it did not dissolve, but it solidified and lost its fluidity. In the freeze-dried product, dissolution was observed when the ratio of α-CD was 25% or less, but when it was 50-60%, it solidified without dissolving. When it was 65% or more, it solidified, but it easily disintegrated and regained its fluidity. The water absorption rate differed between the powder-powder mixture and the freeze-dried product; when it was 2.8%-4.6% for the powder-powder mixture, it was 6.7-9.5% for the freeze-dried product, and the amount of water absorption was greater. If it was left for a long time, it would repeatedly absorb and release moisture depending on the ambient temperature.

The state of the powder mixture after 48 hours is shown in Figures 17 and 18. The state of the freeze-dried product after 48 hours is shown in Figures 19 and 20.

<Comparative test between LS-55P and LS-55L>
LS-55P (LS 55% or more, sucrose 10% or less, lactose 25% or less) and LS-55L (LS 55% or more, sucrose 25% or less, lactose 10% or less) are powder and liquid products with different ratios of sucrose and lactose. The powder product has a higher ratio of lactose, which is easier to powderize. To see if the effect of α-CD differs between the powder and liquid products, the hygroscopicity was compared at the same ratio of LS and CD per solid content. The test was carried out at room temperature with a humidity of 45-60%.

(Results) The results are shown in Table 6. Even if the lactose to sucrose ratio was changed, the same effect was observed as long as the CD to LS ratio was the same.

<Micrographs of freeze-dried LS and freeze-dried LS-α-CD>
To compare the physical structures of the freeze-dried LS product and the product obtained by dissolving LS and α-CD and freeze-drying them, micrographs of both were taken, which are shown in Figures 21 to 24.

Figure 21 shows a micrograph of pulverized freeze-dried LS-55P. As shown in the photo, the product has an irregular shape with sharp angles, but when left at room temperature for an hour in a natural atmosphere, LS absorbs moisture, changes to a rounded shape, and dissolves (Figure 22). α-CD and K-50, which are not hygroscopic, remain irregular with sharp angles even after several days.

Equal amounts of LS-55P and α-CD were dissolved in Bx. 30 and freeze-dried. A micrograph (Figure 23) of this product resembled that of freeze-dried LS, but when it was left at room temperature for a week in an undisturbed atmosphere and then examined under a microscope (Figure 24), most of the pieces maintained their sharp edges, and some of them absorbed water and became rounded, but they had not yet dissolved. It is believed that the α-CD, which maintains its sharp edges, prevents the LS from absorbing more moisture. This effect was apparent when the LS was dissolved in water and freeze-dried.

<Effectiveness test on various oligosaccharides>
The following samples were used to test the improvement of hygroscopicity of α-CD to various oligosaccharides. Sample: α-CD (Dexpearl α-100 Lot. 601167)
LS-55L
Fructooligosaccharides (Nihon Oligo's Fructooligosaccharides: Nihon Oligo Co., Ltd.)
Galactooligosaccharide (King of Oligosaccharides: Nisshin Sugar Co., Ltd.)
Isomaltooligosaccharide (Oligotime: Showa Sangyo Co., Ltd.)

(Method) The solid contents of each oligosaccharide and α-CD were mixed in ratios of 50:50, 40:60, and 30:70, dissolved in approximately Bx. 30, and then freeze-dried. 5 g of each was placed in a weighing dish (made of plastic) and left to stand in a room with a humidity of 59% to 70%, and the weight change and changes in state due to moisture absorption were observed.

(Results) After 24 hours of storage, all of the liquid oligosaccharides mixed with α-CD and freeze-dried showed solidification on the surface and lost their fluidity, but maintained their powdery state, and those with a high α-CD ratio of 70% easily dissolve and regained fluidity. By placing them in a high humidity environment, moisture absorption progressed, and after 34 hours, some of the LS with 50% α-CD and isomaltooligosaccharides had dissolved, and after 48 hours the dissolved parts had hardened. Galactooligosaccharides maintained a moist powdery state on the surface and did not dissolve. Fructooligosaccharides maintained their powdery state, but the surface had solidified and they could not be easily dissolved.

The results are shown in Tables 7, 8, and Figure 25.

The present invention is capable of improving the solubility of β-CD, which has low solubility in water, by mixing it with α-CD. According to the present invention, the solubility of β-CD can be improved in a safe and simple manner without chemical treatment such as mixing with sugars, chemically modifying it, or adding sugars such as maltose. As a result, it becomes possible to use β-CD, which has been recognized as effective in the food, cosmetics, and other fields, at high concentrations or in the form of a concentrated solution, which brings about great economic benefits.

The present invention improves the solubility of β-CD, which has low solubility in water, by using α-CD. The water used here refers to room temperature water that is neither heated nor cooled, and the temperature can be determined as appropriate within the scope of the technical common sense of those skilled in the art. In the examples, water at 25°C was used, but the temperature is usually within the range of 18 to 28°C. Room temperature can also be determined as appropriate within the scope of the technical common sense of those skilled in the art. However, it must be within the range in which the effects of the present application are achieved.

In addition, the present invention makes it possible to improve the hygroscopicity of oligosaccharides such as LS by mixing them with α-CD, dissolving them as necessary, and drying them. As a result, it becomes possible to maintain and distribute oligosaccharides, which have been found to be effective in a variety of fields and applications, in a powdered state rather than a liquid, and to commercialize them in bulk as powdered products, which brings about great economic benefits.

The present invention can be summarized as follows.
That is, the present invention provides a simple method for increasing the solubility of β-cyclodextrin in water.
The solution to this problem is realized by mixing α-cyclodextrin with β-cyclodextrin or producing a composition containing them. The solubility of β-cyclodextrin can also be improved by determining the mixing ratio of β-cyclodextrin and α-cyclodextrin or by adjusting Bx.
This makes it possible to use β-cyclodextrin in the form of a highly concentrated, strong solution, thereby enabling the effectiveness of β-cyclodextrin to be further exerted in various fields.

Additionally, the present invention provides a simple method for improving the hygroscopicity of oligosaccharides.
The solution to this problem is to mix α-cyclodextrin with oligosaccharides or to produce a composition containing them. The effect of improving hygroscopicity can also be further improved by mixing the two, dissolving them in water, and drying them.
This makes it possible to use oligosaccharides in a powdered state, thereby enabling the effectiveness of oligosaccharides to be further demonstrated in various fields.

Claims (4)

A method for increasing the solubility of β-cyclodextrin in water by mixing 23 to 60 % of β-cyclodextrin and 40 to 77% of α-cyclodextrin (excluding those containing components other than β-cyclodextrin and α-cyclodextrin) . A method for increasing the solubility of β-cyclodextrin in water by producing a composition by mixing 23 to 60 % of β-cyclodextrin and 40 to 77% of α-cyclodextrin (excluding those containing components other than β-cyclodextrin and α-cyclodextrin) . The method according to any one of claims 1 and 2, further comprising adjusting Bx. to 40 to 55. A method for producing a composition which enhances the solubility of β-cyclodextrin in water (excluding those which contain components other than β-cyclodextrin and α-cyclodextrin), comprising mixing and dissolving 70 to 80% α-cyclodextrin and 20 to 30% β-cyclodextrin, filtering the mixture , and then spray-drying the mixture.