JPH0678225B2 - Dehydrated medicine and its manufacturing method - Google Patents

Description

TECHNICAL FIELD The present invention relates to a dehydrated drug for promoting health, treating injuries and diseases, and promoting recovery, and a method for producing the same.

More specifically, by incorporating crystalline α-maltose into a hydrous drug selected from hydrous pharmaceuticals, hydrous raw materials and hydrous processed intermediates, crystalline α-maltose captures water in the hydrous substance for dehydration. At the same time, the present invention relates to a dehydrated drug containing crystalline α-maltose converted to β-maltose hydrous crystal and containing the same, and a method for producing the dehydrated drug.

(General technology) Conventionally, in order to promote health, treat illnesses, and promote recovery,
Various medicines such as nutrients, bioactive substances, and bactericides are used.

In general, the water content of nutrients and the like has a great influence on not only its physical properties but also its storage period. Hydrous nutrients are susceptible to microbial contamination, as well as hydrolysis, rancidity,
Susceptible to deterioration such as browning.

Usually, to extend the shelf life of hydrous nutrients, for example,
Various dehydration methods such as sugar pickling, salt pickling and drying are adopted.

However, sugar is too sweet to meet recent tastes, is a main inducer of caries, and has a drawback that it causes an increase in blood cholesterol when taken in large amounts.

It has also been pointed out that excessive intake of salt is a major cause of adult diseases such as hypertension and cancer, and instructions have been given to reduce its intake as much as possible.

Furthermore, in the drying method, deterioration of quality in the process is unavoidable, and it is the current situation that only nutrients with poor flavor can be obtained.

Further, for example, in the case of a physiologically active substance agent containing lymphokine, hormones, vitamins, probiotic agents, enzymes, antibiotics, etc., it is unstable in the presence of high water content,
In order to improve its stability, it is commercialized by a drying method such as heat drying and vacuum drying in the presence of a large amount of stabilizer.

What is used as this stabilizer is albumin,
There are water-soluble polymer compounds such as casein, gelatin and hydroxyethyl starch.

However, it is extremely difficult to dry in the presence of a stabilizer such as a water-soluble polymer compound, and not only a great amount of energy is wasted, but also the obtained dried product becomes sparingly water-soluble or the activity of the physiologically active substance is reduced. There is a risk of causing it.

(Problems to be solved by the invention) The present inventors have focused on maltose for the purpose of eliminating the drawbacks of conventional dehydration methods for pharmaceuticals for health promotion, treatment of injury and illness, and promotion of recovery, I researched the utilization.

As a result, crystalline α-maltose can be converted into β-maltose hydrated crystals by including them in hydrous nutrients, hydrous substances such as hydrous physiologically active substances, etc., so that crystalline α-maltose acts as a strong dehydrating agent. The present invention has been completed by finding out and confirming that a stable drug product can be easily produced without causing deterioration of quality.

The present invention focuses on crystalline α-maltose, which has never been noticed as a dehydrating agent in the past.
-The present invention provides a method for dehydrating a water-containing substance by incorporating maltose as a dehydrating agent.

The method for dehydrating a water-containing material according to the present invention is preferable as a method for dehydrating a water-containing material, particularly a material containing free water different from bound water such as crystal water. When reducing the water contained in the atmosphere in a moisture-proof container containing, for example, further, for example, nutrients, physiologically active substance agents, pharmaceuticals such as bactericides, water content of various hydrates such as raw materials or processing intermediates thereof. It can be advantageously applied when reducing the amount.

When crystalline α-maltose is added to these hydrous substances, the crystalline α-maltose strongly takes up about 5% of its weight of water as water of crystallization of β-maltose hydrous crystals from the hydrous substance. It was found to substantially reduce water content and dehydrate.

For example, in a moisture-proof container containing a dry nutrient such as a liquid edible solid preparation, a crystalline α filled in a moisture-permeable sachet made of paper or the like.
-By allowing maltose to coexist, and by packaging and encapsulating the powdered substance such as powder intestinal preparation and granular digestive agent with crystalline α-maltose, the relative humidity in the container is extremely reduced, It has been found that dried nutritional supplements, powdered products, etc. can be maintained with high quality and stability for a long time.

At this time, the crystalline α-maltose traps water to form β-maltose.
During the conversion to maltose hydrous crystals, even after the conversion, it does not become sticky or run, there is no risk of contaminating the dry nutritional supplement or the moisture-proof container. Can prevent binding.

Furthermore, maltose itself is a non-toxic, non-harmful natural sweetener with no danger.

Further, for example, in the case of liquids such as fresh cream and egg yolk, and high-moisture nutrients such as basting, by including crystalline α-maltose and converting it into β-maltose hydrous crystals, the water content is substantially reduced. It is possible to very easily produce a high-quality dehydrated nutritional product having a reduced content, such as a nutritional product in the form of a musket or a powder. Since this method does not require harsh conditions such as heating and drying, it has a feature that liquid or paste-form high moisture nutrients can be easily converted into dehydrated nutrients without being deteriorated.

At this time, crystalline α-maltose is added in an amount equal to or more than the amount of water contained in these raw materials to obtain crystalline α-maltose.
Maltose was partially converted to β-maltose hydrous crystals, in other words, to obtain a dehydrated nutrient containing crystalline α-maltose together with β-maltose hydrous crystals,
When this is sealed in a moisture-proof container, the water in the atmosphere inside the container is captured and dehydrated by the crystalline α-maltose as crystal water of β-maltose hydrous crystals, and the relative humidity is extremely reduced, so that the inside of the container is highly advanced. It has been found that it can be kept dry.

As a result, the dehydrated nutrient obtained by the method of the present invention,
It was found that not only the prevention of microbial contamination but also the prevention of deterioration such as hydrolysis, rancidity and browning, and the stable maintenance of high-quality products with good flavor for a long period of time.

Further, lymphokines, aqueous solutions of antibiotics, medicinal ginseng extract, also in the case of paste-like physiologically active substances such as soft-shelled turtle extract, by including crystalline α-maltose in these to convert to β-maltose hydrous crystals,
A high-quality dehydrated physiologically active substance agent with substantially reduced water content, for example, a physiologically active substance agent in the form of a musket, a powder, or the like can be very easily produced.

This method does not require harsh conditions such as heat drying,
Moreover, since crystalline α-maltose acts not only as a dehydrating agent but also as a stabilizer, a dehydrating physiologically active substance agent of high quality and stable can be produced.

Also, since it is not necessary to worry about wasting energy for drying the stabilizer such as water-soluble polymer compound,
By appropriately using it as necessary, it is also possible to advantageously carry out the production of a dehydrated physiologically active substance agent having higher quality and stability.

Further, for example, a certain amount of crystalline α-maltose is placed in a vial, and an aqueous solution containing physiologically active substances such as lymphokines and hormones is added to the crystalline α-maltose.
-It is also possible to advantageously carry out the addition of an amount less than the amount of water required for converting maltose to β-maltose hydrous crystals, and tightly stopper to produce a solid preparation for injection or the like.

In this case, it has been found that crystalline α-maltose can not only dehydrate the aqueous solution containing the physiologically active substance but also dehumidify and dry the atmosphere in the vial.

As a result, the dehydrated pharmaceutical product obtained by the present invention is characterized in that not only the manufacturing process thereof is easy, but also its high quality can be stably maintained for a long period of time, and further, it is rapidly dissolved in water during use. It was also found to have.

As described above, the dehydrating agent using the crystalline α-maltose of the present invention is edible unlike the conventionally known dehydrating agents such as silica gel and calcium oxide, and can be metabolized to provide nutrition. It can be advantageously used not only as a sugar dehydrating agent but also as a stabilizer for various physiologically active substances.

Prior to the present invention, the present inventors have studied a method for producing crystalline α-maltose, particularly crystalline α-maltose powder.

First, as a result of detailed examination of the raw material maltose for producing the crystalline α-maltose powder, it was found that high-purity maltose having a solid content of 85 w / w% or more is suitable.

The high-purity maltose as a raw material may be a commercially available β-maltose hydrous crystal, or may be prepared by saccharifying starch according to a conventional method.

As a method for preparing high-purity maltose from starch, for example, β-amylase is produced by allowing β-amylase to act on gelatinized or liquefied starch disclosed in JP-B-56-11437 and JP-B-56-17078. A method for separating high-purity maltose by separating maltose from polymer dextrin, or, for example, Japanese Patent Publication No. 47-13089 and Japanese Patent Publication No. 54-3938.
There is a method, for example, in which gelatinized or liquefied starch is reacted with a starch debranching enzyme such as isoamylase and pullulanase and β-amylase to collect high-purity maltose, which is disclosed in, for example, JP-A-Publication.

Further, contaminating sugars such as maltotriose contained in the high-purity maltose obtained by these methods include, for example, Japanese Patent Publication
56-28153 publication, JP-B 57-3356 publication, JP-B 56-2
The maltose is produced by reacting the enzyme disclosed in Japanese Patent No. 8154 or the like, and further, for example, JP-A-58-23.
It is also convenient to further increase the maltose purity by a method such as removing contaminating sugars by a column fractionation method using a salt-type strongly acidic cation exchange resin disclosed in Japanese Patent Publication No. 799, etc. Further, this fractionation method may be a fixed bed method, a moving bed method, or a simulated moving bed method.

In order to produce crystalline α-maltose powder from high-purity maltose having a solid content of 85 w / w% or more thus obtained, for example, these high-purity maltose have a water content of about 10 w / w.
%, Preferably 2.0 w / w% or more and less than 9.5 w / w% of high-concentration syrup, and the syrup is mixed with seed crystals at 50 ° C. or higher.
It may be produced by crystallizing crystalline α-maltose while maintaining the temperature range of 130 ° C.

Crystalline α-maltose does not substantially crystallize at a water content of 10 w / w% or more, and particularly at a water content of 12 w / w% or more and less than 25 w / w%,
Rather, it was found that not only the crystalline α-maltose of the seed crystal is likely to dissolve and disappear, but also the β-maltose hydrous crystal is more likely to crystallize. It was also found that crystallization of crystalline α-maltose from a high-concentration syrup having a water content of less than 2.0 w / w% was relatively slow.

The temperature during crystallization is preferably in the range of 50 ° C to 130 ° C, particularly preferably 60 ° C to 120 ° C. 50
It was found that at a temperature of less than 0 ° C, crystallization of crystalline α-maltose was extremely slow, which was unsuitable for industrial practice.

Further, it was found that at a temperature above 130 ° C., not only the crystallization is slow, but also the coloring during the crystallization is remarkable, which is unsuitable as a method for producing crystalline α-maltose powder.

Therefore, in order to crystallize crystalline α-maltose, a high-concentration syrup having a water content of high-purity maltose of less than 10 w / w%,
It is important to crystallize in the presence of seed crystals while maintaining the temperature range of 50 ° C to 130 ° C. At this time, a method of making high-purity maltose into a high-concentration syrup having a water content of less than 10 w / w% is, for example, a maltose content of 85 w / w% or more per solid of a commercially available β-maltose hydrous crystal is heated and dissolved in a small amount of water. A high-concentration syrup having a water content of less than 10 w / w% may be used, or a high-purity maltose aqueous solution having a maltose content of 85 w / w% or more per solid matter obtained by saccharifying starch is concentrated under reduced pressure to have a water content of 10 w. High-concentration syrup of less than / w% may be used, and the water content in these high-purity maltose is 10 w / w.
% To less than 35 w / w% aqueous solution may be formed into high-concentration syrup droplets having a water content of less than 10 w / w% by a spray drying method or the like.

Further, to crystallize crystalline α-maltose in the presence of seed crystals, with respect to high-concentration syrup solids of high-purity maltose, usually 0.001 w / w% or more and less than 100 w / w%, desirably, It suffices if crystalline α-maltose can be crystallized by coexisting with seed crystals of crystalline α-maltose of 0.1 w / w% or more and less than 20 w / w%, and as a method thereof, for example, water of high-purity maltose 10 w / w % High-concentration syrup to knead seed crystals for crystallization, or high-purity maltose water content
Seed crystals are mixed with syrup of 10w / w% or more and less than 20w / w%, and while this seed crystal does not dissolve or disappear, it is crystallized into high-concentration syrup droplets with a water content of less than 10w / w% by a spray drying method. Or even more, high-purity maltose water content of 10w / w% or more 35w / w%
A syrup having a water content of less than 10 w / w% is formed into a syrup droplet by a spray drying method, and a seed crystal is brought into contact with the syrup to crystallize.

In addition to the above method, it is also advantageous to promote crystallization under pressure. In particular, it is convenient to apply a pressure of about 5 kg / cm ² or more when crystallizing α-maltose and during eutectic. Therefore, the method for producing the crystalline α-maltose powder using an extrusion granulator or the like, which requires pressurization and compression, can be advantageously carried out.

It was also found that it is possible to advantageously carry out crystallization while promoting the crystallization of the musket during crystallization. The drying method can be appropriately selected under normal pressure, reduced pressure, or increased pressure, and a stationary state or a fluidized state.

The method for promoting the crystallization of these crystalline α-maltose has a content of the optical isomer α-maltose of the present invention of 55 w / w%.
The time to reach the above can be shortened to about 4/5 to 2/5, not only increasing the production efficiency of the crystalline α-maltose powder, but also extremely increasing the coloring degree of the crystalline α-maltose powder. It is advantageous as a method for mass production of reduced and high quality crystalline α-maltose powder.

Further, a method in which two or more of these methods are combined, for example, a eutectic by a method such as the above method from a high-concentration syrup having a water content of high-purity maltose of less than 10 w / w% to give an optical isomer α-
A maltose with a maltose content of more than 48w / w% is formed, and then it is molded into various shapes such as powder, strands, blocks, etc., and is aged while being crystallized and dried while being maintained in the temperature range of 50 ° C to 130 ° C. A method for producing a crystalline α-maltose powder having an isomer α-maltose content of 55 w / w% or more can also be carried out very advantageously.

As the aging condition, usually, in the temperature range of 50 ° C to 100 ° C, about 0.1 to 24 hours, in the temperature range of more than 100 ° C and 130 ° C, about 0.5 to 18 hours, preferably higher temperature,
It has been found that under severe conditions for a long time, the degree of coloring of the crystalline α-maltose powder obtained increases and the commercial value is impaired. Crystallization under pressure and / or while drying during aging can promote crystallization of crystalline α-maltose and significantly shorten the aging time, so that the crystalline α-maltose powder It is convenient as a mass production method.

Further, as a method for producing a crystalline α-maltose powder having an optical isomer α-maltose content of 55 w / w% or more, for example, an extrusion granulation method, a block pulverization method, a spray drying method, a fluidized granulation method, etc. is there.

In the case of the extrusion granulation method, for example, while maintaining a high-concentration syrup having a water content of high-purity maltose of less than 10 w / w% in a temperature range of 50 ° C to 130 ° C, a seed crystal of crystalline α-maltose is added thereto. The mixture is kneaded and assisted to give a mass kit having a content of the optical isomer α-maltose of more than 48 w / w%, and the granulated mass kit or granular powder obtained by subjecting this to an extrusion granulator is heated at a temperature of 50 ° C to 130 ° C. Crystallized and aged while drying while maintaining the range, and the optical isomer α-maltose content was 55 w /
Collect w% or more crystalline α-maltose powder.

Further, high-concentration maltose water content of less than 10w / w% high-concentration syrup, extruded without coexisting seed crystals, granulated, contact the resulting high-concentration syrup droplets crystalline α-maltose seed crystals, While maintaining the temperature range of 50 ℃ ~ 130 ℃, while crystallizing and aging while drying, the optical isomer α-
A crystalline α-maltose powder having a maltose content of 55 w / w% or more can also be collected.

In the case of the block pulverization method, for example, a high-concentration maltose with a high-concentration syrup having a water content of less than 10 w / w% is taken in an auxiliary crystallizer, and while maintaining the temperature range of 50 ° C. to 130 ° C., crystalline α-maltose is added thereto. Seed crystals of (1) are mixed with each other to form a mass kit having a content of the optical isomer α-maltose of more than 48 w / w%.
C. to 130.degree. C. while crystallizing and solidifying while maintaining the temperature range, the resulting block is crushed with a cutting machine, a hammer mill, etc., dried and sieved to obtain the optical isomer α-maltose content.
55 w / w% or more of crystalline α-maltose powder is collected.

In the case of the spray drying method, for example, the water content of high-purity maltose is about 10 w / w% or more and less than 20 w / w% and the crystalline α-
Seed crystals of maltose are mixed and spray dried by a high-pressure nozzle method or a rotating disk method as quickly as possible so that the seed crystals do not dissolve and disappear to form syrup droplets with a water content of less than 10 w / w%. Crystallization aged while crystallizing and aging while keeping the temperature in the range of ℃ to 130 ℃, and collecting crystalline α-maltose powder having optical isomer α-maltose content of 55 w / w% or more.

Further, in the case of the fluidized granulation method, for example, a syrup having a water content of high-purity maltose of 15 w / w% or more and less than 35 w / w% is directed toward the seed crystals of crystalline α-maltose which is fluidized in advance. , Water content less than 10w / w% by spray-drying to form a high-concentration syrup droplet, and aging while crystallization while drying while maintaining this in the temperature range of 50 ° C to 130 ° C, the optical isomer α-maltose content is 55 w / w% or more of crystalline α-maltose powder is collected.

It is also advantageous to carry out continuous production of crystalline α-maltose by continuously turning a part of the crystalline α-maltose obtained as described above into a seed crystal.

The crystalline α-maltose powder having an optical isomer α-maltose content of 55 w / w% or more of the present invention produced in this manner is a white powder having an elegant and low sweetness, its water content is low, and substantially Anhydrous, usually by Karl Fischer
It is less than 3w / w%, preferably less than 2w / w%, and its fluidity is slightly different depending on the shape and size of powder particles, the difference in optical isomer α-maltose content, etc. Is.

The melting point is 121 to 125 of β-maltose hydrous crystal.
Much higher than ℃, 130 ℃ or more, especially in the case of crystalline α-maltose powder with an optical isomer α-maltose content of 60 w / w% or more, there is a risk of sticking or solidification at about 140 ℃ or more. No crystalline powder with sufficient fluidity.

The crystalline α-maltose powder thus obtained is
When this is contained in a water-containing material such as food, pharmaceuticals, cosmetics, industrial chemicals, etc., the water content contained therein is β-.
It was found that the maltose hydrated crystals were captured and fixed as water of crystallization and acted as a strong dehydrating agent for the hydrated substance.

Crystalline α-maltose is not only water-containing crystals (Hayashibara Co., Ltd., registered trademark Sanmalto) that are commercially available in the past, but not only water but also an organic acid aqueous solution, a salt aqueous solution, a protein aqueous solution, an emulsion, and an alcohol. It was found that it can be rapidly dissolved in a high concentration in various aqueous solutions such as an aqueous solution. This property is convenient for using crystalline α-maltose as a dehydrating agent to produce various dehydrated articles with reduced water content from various hydrates.

As the dehydrating agent of the present invention can be advantageously applied, when dehumidifying and drying the atmosphere in the moisture-proof container, further, heat-drying, water-containing substances that easily accompany deterioration in the process such as vacuum drying or water-containing difficult to dry From things etc. to high quality mask kit,
There are cases where a dehydrated article such as powder is manufactured.

When dehumidifying and drying, for example, not only can be used to prevent moisture absorption of dry nutrients, etc., further, a powdery substance that easily absorbs moisture and solidifies, for example, powdered yeast extract, powdered milk, powdered yogurt, Powdered cheese, powdered juice, powdered herbs, powdered vitamins, granule soup, granule broth,
The relative humidity inside the packaging container is reduced by blending crystalline α-maltose in a powdered material such as fish meal, blood meal, bone meal, powdered lactic acid bacteria preparation, powdered enzyme preparation, granule digestive preparation, etc. Since it is possible to prevent adhesion and solidification of the product, it can be used for the purpose of maintaining high quality with good fluidity immediately after production for a long period of time.

When dehydrating a water-containing material, for example, an animal,
It can be advantageously used for dehydrating various hydrates such as plants, organs derived from microorganisms, tissues, cells, grinds, extracts, components, or preparations thereof.

For example, in the case of nutritional supplements, raw materials or processed intermediates thereof, raw fruits, juices, vegetable extracts, soymilk, nut paste, gelatinized starch paste and other agricultural products, raw eggs, lecithin,
Milk, fresh cream, yogurt, butter, livestock products such as cheese, seafood such as sea urchin paste, oyster extract and sardine paste, sweeteners such as maple syrup and honey, alcohol such as sake, wine, medicinal liquor, etc., liquid or paste A stable and high-quality dehydrated nutrient can be easily produced from the substance.

In the case of physiologically active agents, raw materials or processed intermediates thereof, lymphokine-containing solutions such as interferon, lymphotoxin, Tumor necrosis factor, macrophage migration inhibitory factor, colony stimulating factor, transfer factor, interleukin II, insulin, growth, etc. Hormones, prolactin, erythropoietin, hormone-containing liquids such as follicle-stimulating hormone, BCG vaccine, Japanese encephalitis vaccine, measles vaccine, live polio vaccine, smallpox seedlings, tetanus toxoid, hub antitoxin, liquid containing biologics such as human immunoglobulin, penicillin, Erythromycin, chloramphenicol, tetracycline, streptomycin, kanamycin sulfate and other antibiotic-containing liquids, thiamine, riboflavin, ascorbic acid, liver oil, carotenoids, Lugosterol, vitamin-containing liquid such as tocopherol, lipase, elastase, urokinase, protease, β-amylase, isoamylase, glucanase, enzyme-containing liquid such as lactase, ginseng extract, soft-shelled turtle extract, extracts such as chlorella extract, virus, Stable and high-quality dehydrated physiologically active substance agents can be easily produced without losing the active ingredient and activity of liquid bacteria or paste such as lactic acid bacteria, live bacteria paste such as yeast and royal jelly.

Further, by dehydrating the raw egg, lecithin, fresh cream, honey, licorice extract, fragrance, coloring agent, enzyme, etc., it can be advantageously used as a high-quality skin-care agent, hair-restoration agent, hair-growth agent and the like.

When the dried product is an enzyme, it can be advantageously used as a catalyst for processing foods, pharmaceuticals, industrial raw materials, etc., as a therapeutic agent, a digestive agent, etc., and also as an enzyme detergent.

As a method for containing crystalline α-maltose in a water-containing material, a known method such as kneading, kneading, dissolving, permeating, spraying, coating, spraying or pouring is appropriately used until the intended dehydrated article is completed. To be chosen.

The amount of crystalline α-maltose contained in the hydrate varies depending on the amount of water contained in the hydrate and the properties of the intended dehydrated article. If necessary, the hydrate is partially dehydrated by other known methods. Alternatively, crystalline α-maltose may be added after concentration, and it is usually 0.01 to 500 parts by weight, preferably 0.1 to 100 parts by weight with respect to 1 part by weight of the hydrate. At this time, in order to further improve the quality of the obtained pharmaceutical product, it is also possible to advantageously use a suitable flavoring agent, coloring agent, flavoring agent, stabilizer, extender and the like in combination.

In particular, regarding the stabilizer, since the present invention is a strong dehydration method using crystalline α-maltose, it is not necessary to limit it to a low molecular weight compound such as an antioxidant, and it is conventionally difficult to dry it. Polymeric compounds, for example, soluble starch, dextrin, cyclodextrin, vullan, erucinan, dextran, xanthan gum, gum arabic, locust bean gum, guar gum, tragacanth gum, tamarind gum, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxyethyl starch, pectin, agar, Substances such as gelatin, albumin and casein can also be advantageously used as stabilizers.

When using these water-soluble polymer compounds, for example,
In a liquid or paste-like hydrate, a water-soluble polymer compound is uniformly dissolved in advance, and then crystalline α-maltose is mixed therein, and the resulting mixture is uniformly mixed by a method such as kneading to give a fine β- A dehydrated article obtained by precipitating maltose hydrous crystals is obtained. This product has a fragrance component derived from a hydrate, an active ingredient, etc., coated with a film of a water-soluble polymer compound, or is encapsulated together with fine β-maltose hydrated crystals in microcapsules surrounded by the film. ,
Further, when cyclodextrin is used, it forms an inclusion compound, etc., and its volatilization and quality deterioration are prevented, and therefore, it is extremely excellent in stable retention of the aroma component derived from the water-containing substance and the active ingredient. The cyclodextrin is not limited to high-purity cyclodextrin, and low-purity cyclodextrin that is difficult to dry and difficult to powder, for example, starch syrup partial hydrolyzate containing various cyclodextrins together with a large amount of maltodextrin. Can also be used to advantage.

Various methods can be adopted as the method for producing the dehydrated article of the present invention, especially the powdered article. For example, crystalline α-maltose is uniformly added to a water-containing substance having a relatively high water content such as pharmaceuticals, their raw materials or processing intermediates so that the water content is about 30 w / w% or less, preferably about 5 to 25 w / w%. After containing it, it is left in a vat or the like for about 1 to 10 days at about 10 to 50 ° C., for example, room temperature to be converted into β-maltose hydrous crystals, and solidified into, for example, a block shape, which is cut, pulverized, or the like. It may be manufactured by the method. If necessary, a drying step, a classification step, etc. can be added after the powdering step such as cutting and crushing.

Alternatively, the powder product can be directly produced by a spraying method or the like. For example, while flowing the crystalline α-maltose powder, a predetermined amount of a liquid or pasty water-containing substance is sprayed and brought into contact with the powder to granulate it, and then aged at about 30 to 60 ° C. for about 1 to 24 hours. Or to convert it into β-maltose hydrous crystals, or by mixing crystalline α-maltose with a liquid or pasty hydrous material, kneading, etc., immediately or by starting conversion to β-maltose hydrous crystals. A method of producing a powdered product by similarly aging the powdered product obtained by spraying and converting the powdered product into β-maltose hydrous crystals is suitable as a mass production method.

In the case of this spraying method, in order to promote the conversion of crystalline α-maltose into β-maltose hydrous crystals, crystalline α-maltose is used.
It is also advantageous to coexist with a seed crystal of β-maltose hydrous crystal of about 0.01 to 10 w / w% with respect to maltose to shorten the aging period. If necessary, it is optional to use a known drying method together with the use of a dehydrating agent.

The powdered dehydrated drug thus obtained is used as it is or, if necessary, in combination with a filler, an excipient, a binder, a stabilizer, etc., and further granules, tablets, capsules, It can be freely formed into a suitable shape such as a rod shape, a plate shape, or a cubic shape.

Further, granules, pharmaceutical intermediates such as plain tablets are used as cores, and about 70 to 95 w / w% aqueous solution of crystalline α-maltose, preferably, an aqueous solution in which an appropriate amount of a binder such as a water-soluble polymer coexists. It can also be advantageously carried out to produce a sugar-coated product by coating with the above, and then converting to β-maltose hydrous crystals and crystallizing.

Further, crystalline α-maltose is mixed with a high-moisture hydrate, which is contained by a method such as kneading, when crystalline α-maltose is converted into β-maltose hydrous crystals and dehydrated, β
Expands its volume as it transforms into maltose hydrous crystals. When the expansion is remarkable, it reaches about 1.5 to 4.0 times. In this way, the one that expands and solidifies has a lower hardness compared to the one that expands less, it is easier to pulverize, the wear of the cutting machine, the crusher, etc. is less, and the power consumption of the power is also consumed. It has features that can save a lot of money.

Also, by utilizing this expansion phenomenon, dehydrated articles of various shapes can be manufactured. For example, flowers, birds, fish, plastic containers having various shapes such as dolls, and the like, containing high-moisture hydrate containing crystalline α-maltose, allowed to stand at room temperature for about 5 to 90 hours to expand, By solidifying, dehydrated articles of various shapes can be obtained. If necessary, in order to further accelerate this expansion, a solvent that easily vaporizes such as alcohol, a foaming agent that generates carbon dioxide gas, etc. may be contained together with the crystalline α-maltose, and slightly heated.
It may also be exposed to a steam atmosphere in order to accelerate the conversion to β-maltose hydrous crystals and reduce the time.

The dehydrated articles in various shapes obtained in this manner can be advantageously used for medicines and the like that can enjoy the shapes.

In addition, starch generally requires a large amount of water for its swelling and gelatinization. Therefore, gelatinized starch is extremely susceptible to microbial contamination. Crystalline α-maltose can be advantageously used as a dehydrating agent for such gelatinized starch.
For example, gelatinized starch such as fertilizer can contain crystalline α-maltose and convert it into β-maltose hydrous crystals, whereby the water content is substantially reduced and microbial contamination can be prevented.

In addition, crystalline α-maltose mixes easily and uniformly with gelatinized starch and also acts as an antiaging agent, so that the product life of various processed nutrients containing gelatinized starch is significantly extended. be able to.

Further, crystalline α-maltose can be obtained, for example, from Japanese Examined Patent Publication No. 52-48.
Unlike the maltose syrup powder disclosed in the 198 publication, it has a high affinity for alcohol. Due to this property, it can be advantageously used as a dehydrating agent for water contained in alcohols such as methanol, ethanol, butanol, propylene glycol, glycerin, polyethylene glycol, or alcohol-soluble substances. For example, dehydration of alcohol-containing hydrates such as medicinal liquor with crystalline α-maltose, and the resulting β-maltose hydrate crystals, the active ingredient, a musket form retaining the aroma and the like, powdered products and the like can be advantageously produced. can do.

Further, an alcohol solution such as iodine is mixed with crystalline α-maltose, and an aqueous solution containing a water-soluble polymer or the like is added to the mixture to convert it into β-maltose hydrous crystals, thereby stabilizing the active ingredients such as iodine. It is also possible to advantageously carry out production of a musket-shaped salve or the like which retains and has an appropriate viscosity, extension and adhesiveness.

In addition, crystalline α-maltose has a surprisingly large lipophilicity even though it is a hydrophilic sugar.

From this property, crystalline α-maltose is an oil-soluble substance,
It can also be advantageously used as a dehydrating agent for water contained in emulsions and latexes.

Oil-soluble substances, for example, soybean oil, rapeseed oil, spicy oil, sesame oil, safflower oil, palm oil, cocoa butter, beef tallow, lard, chicken oil, fish oil, fats such as hydrogenated oil, citrus essential oils, flower essential oils, spices Oil-soluble spices such as oil, peppermint oil, spearmint oil, cola nut extract, coffee extract, oil-soluble colorants such as β-carotene, paprika dye, anato dye, chlorophyll, liver oil, vitamin A, vitamin B ₂ butyrate , Vitamin E, Hitamin K, Hitamin D and other oil-soluble vitamins, Estrogen, Progesterone, Androgen, Prostaglandin and other oil-soluble hormones, Linoleic acid, Linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid and other highly unsaturated compounds Desorption that strongly captures even a small amount of water contained in fatty acids, etc. It can be advantageously used as agents.

The oil-soluble substance dehydrated by crystalline α-maltose is
It is of high quality and has the characteristic of being less susceptible to quality deterioration such as hydrolysis and deterioration.

Further, a crystalline α-maltose is impregnated with a water-containing oil-soluble substance, an emulsion, a latex, etc., and crystalline α-maltose is converted into β-maltose hydrous crystals by mixing, etc., a powdered nutritional supplement, a powdered vitamin, It can also be advantageously carried out to produce a physiologically active substance agent such as a hormone.

In this case, the crystalline α-maltose acts not only as a dehydrating agent but also as a stabilizer, a retaining agent, an excipient, a carrier or the like after being converted into β-maltose hydrous crystals.

Crystalline α-maltose is also advantageously used in the case of foods containing oil-soluble substances such as chocolate and sand cream that dislike moisture. In this case, not only as a dehydrating agent, but also having good processing suitability, melting in the mouth, flavor and the like is utilized. Furthermore, the obtained product has the characteristic that its high quality can be stably maintained for a long period of time.

As described above, the present invention was achieved by finding that crystalline α-maltose strongly dehydrates the water content of various hydrates, and the crystalline α-maltose is used as a dehydrating agent. By doing so, from a water-containing substance such as a liquid or a paste, its flavor and aroma are not deteriorated and volatilized, and a high-quality nutrient with reduced water content, its active ingredient, and activity are not degraded or degraded. ,
A medicinal product such as a high-quality bioactive substance agent with reduced water content can be advantageously produced.

In addition, crystalline α-maltose is not only the special case described above, but a natural sweetener inherent to maltose, and there is no concern about tooth decay induction, increase in blood cholesterol, and the like. Since it also has properties such as imparting, imparting luster, viscosity, and water retention, it can be advantageously used for the production of orally used nutrients and the like.

Further, crystalline α-maltose is a nutrient that is originally utilized for metabolism of maltose.

When it is used parenterally as an injection, it becomes isotonic at twice the concentration as compared to glucose, so calories can be supplemented at twice the concentration, which requires large calories during surgery. It is suitable as a nutritional supplement for treatment.

Hereinafter, the present invention will be described in detail using experiments.

Experiment 1. Comparison of raw material maltose As raw material maltose, various starch sugar products manufactured by Hayashibara Co., Ltd. shown in Table 1 were used.

Product name Marster , HM-75 and other syrup products
To remove the water, just put it in an evaporator and boil it under reduced pressure.
It was set to 5w / w%.

Product name San Marto , Maltose H, maltose HH,
Powder such as β-maltose hydrous crystals such as maltose HHH
In the case of powdered products, dissolve with heat with a small amount of water, then evaporate
It was taken in a kettle and boiled under reduced pressure to a water content of 4.5 w / w%.

The high-concentration syrup having a water content of about 4.5 w / w% thus obtained was transferred to an auxiliary crystallizer, and in advance, high-purity β-maltose hydrous crystal (maltose HHH) was added at about 50 w / v% hot methanol. Crystalline α-maltose that was crystallized from the solution was added as a seed crystal at 2 w / w%, assisted by stirring for 20 minutes at 120 ° C, then taken out into an aluminum vat and aged at 90 ° C for 16 hours to prepare a block. . Then, it was cooled to room temperature and pulverized to obtain a powder product. Using these powders, CC Sweeley et al.,
Gas chromatography is performed according to the method described in J. Am. Chem. Soc., Vol. 85, 2497-2507 (1963) to determine the content of the optical isomer α-maltose in maltose. , FH Stodola et al., J. Am. Chem. S
oc., Vol. 78, 2514-2518 (1956), using an X-ray diffractometer (manufactured by Rigaku Denki Co., Ltd., trade name Geiger Flex RAD-IIB, using Cu Kα rays). Powder X-ray diffraction was performed to examine the presence or absence of crystals. The results are shown in Table 1. The X-ray diffraction patterns are shown in FIGS. 1 is an amorphous powder having an α-maltose content of 48 w / w%, FIG. 2 is a crystalline powder having an α-maltose content of 55.6 w / w%, and FIG. 3 is an α-maltose content of 61.4 w. / w%
FIG. 4 shows the crystalline powder having a content of α-maltose of 68.7.
FIG. 5 is an X-ray diffraction pattern of the crystalline powder having an α-maltose content of 74.2 w / w%.
As a control experiment, β-maltose hydrous crystal (maltose HHH) Of the amorphous powder obtained by heating and dissolving P.
As a result of line diffraction, the same X-ray diffraction pattern as that shown in Fig. 1 was obtained, and the X-ray diffraction pattern of Fig. 6 was obtained by X-ray diffraction of the raw material β-maltose hydrous crystal (maltose HHH) powder. Was given.

As is clear from the results of Table 1, the precipitation of new crystals was confirmed by X-ray diffraction, and the content of the optical isomer α-maltose was 55 w / w% or more. It has been found that a maltose content of 85 w / w% or more per solid is required.

Experiment 2. Comparison of lipophilicity 2-1 Comparison of oil retaining power Particle size of test No. 1 to 8 prepared by the method of Experiment 1 and sugar (test No. 9) and lactose (test No. 10) About 45-150
Oil retention was compared as a powder of μ. The oil retention is measured according to the method disclosed in JP-A-59-31650.
Weigh 10 g of rapeseed oil into a beaker and add powdered sugar while stirring. This mixture has fluidity as long as the amount of powdered sugar added is small, but as the amount increases, the consistency increases and eventually becomes a lump. If the amount of addition is further increased, the hardness increases, and eventually they do not unite into one and begin to unravel. With this point as the end point, the oil retaining power was determined by the following formula.

The results are shown in Table 2.

2-2 Comparison of emulsifying power The emulsifying power was compared using powders of various sugars having a particle diameter of about 45 to 150 µm prepared by the method of Experiment 2-1.

To measure the emulsifying power, 2 g of soybean oil is placed in a beaker, 2 g of various sugar powders are added thereto, and the mixture is stirred and mixed with a glass rod. The obtained mixture was put in a test tube with a ground stopper, 30 ml of water was added thereto, and the mixture was gently shaken several times by hand to mix, and the mixture was allowed to stand at room temperature overnight.
The water phase of this was visually observed, and the strength of the cloudiness was determined.

In addition, when microscopic observation of the emulsified aqueous phase was observed, the presence of saccharide crystal powder was not observed, and only a large number of oil droplets having a diameter of approximately 2 to 5 μm were observed. The number of oil drops was high.

The results are shown in Table 2.

As is clear from the results in Table 2, the crystalline α-maltose powder was excellent in both oil retaining power and emulsion power, and was found to have remarkable lipophilicity.

Experiment 3. Effect of high-purity maltose syrup water content on crystallization of crystalline α-maltose The raw material maltose was β-maltose hydrous crystalline powder manufactured by Hayashibara Co., Ltd. Maltose HHH (maltose content 99.7w / w%) was used. Then, the influence of the water content of the high concentration syrup on the crystallization of crystalline α-maltose was investigated.

β-maltose hydrous crystal powder is heated and dissolved in a small amount of water,
Then, it was placed in an evaporator and boiled under reduced pressure to prepare syrup of various water contents. Crystalline α-maltose seed crystals were added to this in an amount of 2 w / w% with respect to the syrup solid, and the mixture was agitated at 100 ° C for 5 minutes to assist crystallization. Then, take it out into an aluminum vat and hold it at 70 ℃ for 6
Aged for time to prepare blocks. After cooling this to room temperature, the content of the optical isomer α-maltose was measured.

The results are shown in Table 3.

As is clear from the results shown in Table 3, crystallization of crystalline α-maltose was caused by high-purity maltose syrup water content of 10 w / w%.
It has been found that a syrup of 2.0 w / w% or more and less than 9.5 w / w% is suitable.

Experiment 4 Effect of temperature on crystallization of crystalline α-maltose The raw material maltose is β-maltose hydrous crystal manufactured by Hayashibara Co., Ltd., trade name Maltose H (maltose content 91.5).
w / w%) was used to investigate the effect on the crystallization of crystalline α-maltose.

β-maltose hydrous crystal powder is heated and dissolved in a small amount of water,
Then, it is placed in an evaporator and boiled under reduced pressure to prepare syrup having a water content of 4.5 w / w%, and seed crystals of crystalline α-maltose are added to this syrup solid at 2 w / w% and the mixture is heated at 100 ° C. for 5 minutes. Stir-assisted crystallization, then take out in an aluminum vat, 20 ℃
A block was prepared by crystallization and aging for 16 hours at each temperature of ˜140 ° C., and then the optical isomer α-maltose content was measured.

Furthermore, the degree of coloring of these blocks was measured. The degree of coloring is
The difference in absorbance at 420 nm and 720 nm (A _420-720 ) in a 10 cm cell in a 30 w / v% aqueous solution is shown.

The results are shown in Table 4.

As is clear from the results shown in Table 4, it was found that the crystallization of crystalline α-maltose is preferably carried out in the temperature range of 50 ° C to 130 ° C, and more preferably in the range of 60 ° C to 120 ° C. It was also found that the degree of coloration of crystalline α-maltose varied depending on the crystallization temperature, and increased significantly above 130 ° C. That is, it was found that the coloring degree of the product crystallized at 140 ° C. was about 14 to 20 times as high as 100 ° C. or lower, 7 times as high as 120 ° C. and 3 times as high as 130 ° C. .

Experiment 5. Comparison of Dehydration Ability of Various Sugars Anhydrous glucose, sugar, crystalline α-maltose prepared in Test No. 5 of Experiment 1, or β-maltose hydrous crystal as a raw material thereof was used, and the particle size was about 100- Powdered 150μ, 1g each on a plastic dish with a diameter of 5cm, left in an atmosphere of 25 ° C with a relative humidity of 70%, and measure the water content (%) of these sugars over time to dehydrate. The strength of power was compared.

The results are shown in Table 5.

As is clear from the results in Table 5, crystalline α-maltose was found to act as a powerful dehydrating agent until it trapped about 5 w / w% of its weight of water.

Moreover, when the X-ray diffraction patterns of the respective samples were examined with time, and compared, there was no change in anhydrous glucose, sugar, and β-maltose hydrous crystals. However, it was found that crystalline α-maltose changes by trapping water, is converted into β-maltose hydrous crystals with about 5% of water, reaches equilibrium water, and is stabilized.

Similarly, the same crystalline α-maltose was placed in an atmosphere of 25 ° C., which was conditioned to a relative humidity of 92%, and its water content (%) was measured with time. It was found that even after conversion to water-containing crystals, water was taken in, and equilibrium was reached and stabilized at about 18% water. Also in this case, the phenomenon of maintaining the powder state and getting wet or flowing was not observed.

From this property, crystalline α-maltose can be advantageously used as a dehydrating agent such as a nutritional agent, a drug such as a physiologically active substance agent, its raw material or a processing intermediate.

Experiment 6. Utilization of various sugars in sand cream Sand creams were prepared using various sugars and their dehydration effects were compared.

As the various sugars, the same ones used in Experiment 5 were used.

The preparation method is as follows: Take 425 g of shortening in a mixer, add 500 g of sugar to it and mix, then add a melt of 25 g of pre-prepared soybean oil (white squeezing oil) and 50 g of cocoa butter and whip and sand. It was cream.

In addition, what used the β-maltose hydrous crystal as saccharide could not be mixed, and the sand cream could not be produced.

The obtained sand cream was conditioned to 92% relative humidity 29
The sample was left to stand in a harsh atmosphere of ℃, its water content (%) was measured over time, and the state of the sand cream was observed.

The results are shown in Table 6.

As is clear from the results in Table 6, the sand cream using crystalline α-maltose did not lose its shape even under the severe conditions of 29 ° C. where the relative humidity was adjusted to 92%. -It was found that maltose was converted into β-maltose hydrous crystals, reached equilibrium with atmospheric conditions and stabilized. Based on this fact, the prepared sand cream can be stored in a moisture-proof container by sandwiching it between cookies and biscuits, for example, to capture the moisture in the atmosphere and dehydrate it to reduce the relative humidity of the atmosphere. It was also found that the sand cream can be stably maintained for a long period of time without degrading the quality of the sand cream itself. This property can be advantageously used for the production of a drug containing an oil-soluble substance.

Experiment 7 Comparison of sugar to gelatinized starch Dissolve 400 g of glutinous rice flour with 600 ml of water, pour it into a wooden frame covered with wet cloth, and steam this at 105 ° C for 10 minutes to obtain gelatinized starch.

To this, 800 g of crystalline α-maltose prepared in Test No. 5 of Experiment 1 or β-maltose hydrous crystal which is a raw material thereof was mixed with a mixer, and when the mixture became uniform, further starch syrup was added.
200 g was added, and the mixture was thoroughly kneaded to form a fertilizer, which was then lightly dried with warm air at 40 ° C for 2 hours to obtain a fertilizer.

When this product was left open in a room at 25 ° C and left for 12 days, black mold colonies were observed in those that used β-maltose hydrous crystals, but those that used crystalline α-maltose were observed. , No microbial contamination was observed even after 20 days.

Also, after cutting the thing after 20 days, when observing the cross section, the one using crystalline α-maltose, although the surface layer portion is slightly hardened and crystals are precipitated, the inside is the same as immediately after production. It was semi-transparent and had moderate gloss and viscosity.
From the X-ray diffraction pattern, the crystals in the surface layer were found to be crystalline α-maltose converted into β-maltose hydrous crystals.

On the other hand, in the case of using the β-maltose hydrous crystal, not only the mold was generated on the surface but also the cross section was clouded over the whole layer and was not glossy.

As a result, it was found that crystalline α-maltose acts as a dehydrating agent for gelatinized starch, prevents microbial contamination, and further prevents aging of gelatinized starch.

This property can be advantageously used for manufacturing a pharmaceutical product containing gelatinized starch.

Hereinafter, a method for producing the crystalline α-maltose powder will be described in reference examples.

Reference Example 1 A suspension of 1 part by weight of potato starch and 10 parts by weight of water was mixed with a commercially available bacterial liquefying α-amylase and heated to 90 ° C for gelatinization, and immediately heated to 130 ° C to stop the enzyme reaction, and then DE A liquefied liquid of 0.5 was obtained. This starch liquefaction liquid was rapidly cooled to 55 ° C and then Pseudomonas amyloderamosa ATCC2
Isoamylase (EC3.2.1.6
Add 8) of 100 units per starch roof tile and 50 units of β-amylase derived from soybean (EC3.2.1.2) (trade name # 1500 manufactured by Nagase & Co., Ltd.) to keep the pH at 5.0. It was saccharified for a long time to obtain a high-purity maltose solution having a maltose content of 92.5 w / w% per solid matter, which was decolorized with activated carbon and desalted and purified with an ion exchange resin. After concentrating the maltose solution to a concentration of 75%, place it in a supporting crystal can, add 1% of powdered seed crystals of β-maltose monohydrate crystal to 40 ° C., slowly cool with slow stirring, and allow for 2 days. The mixture was cooled to 30 ° C., mashed with a basket-type centrifuge, and the crystals were sprayed and washed with a small amount of water to obtain high-purity β-maltose hydrous crystals with a purity of 99.0%.

The high-purity maltose thus obtained was dissolved by heating with a small amount of water, then placed in an evaporator and boiled under reduced pressure to give syrup having a water content of 5.5 w / w%. Then transfer to the auxiliary crystal,
Crystalline α-maltose obtained by the method of Experiment 1, Test No. 6 was added to this in an amount of 1 w / w% based on the solid syrup, and the mixture was agitated at 100 ° C. for 5 minutes, and then taken out in a plastic vat to 70 ° A block was prepared by aging crystallization for 6 hours.

Next, this block is crushed by a cutting machine, fluidized and dried, and the optical isomer α-maltose content is 73.3 w / w%, the water content.
0.42 w / w% of crystalline α-maltose powder was obtained in a yield of about 92 w / w% based on the raw material of high-purity β-maltose hydrous crystals.

The product can be advantageously used as a dehydrating agent for hydrous substances such as the drug of the present invention, its raw materials or processed intermediates.

Reference Example 2 The maltose content prepared by the method of Reference Example 1 is per solid matter.
A 92.5w / w% high-purity maltose aqueous solution was concentrated under reduced pressure to a water content of 20w / w%, then sprayed from the nozzle of the spray drying tower with a high-pressure pump from a nozzle, and dried with hot air at 100 ° C while drying the tower. On the moving wire mesh conveyor at the bottom, in advance, let it drop on the flowing crystalline α-maltose powder, while sending hot air at 70 ° C from under the conveyor, gradually moving it outside the drying tower, 60 The powder taken out in a minute was charged into an aging column and aged for crystallization for 4 hours while passing hot air at 70 ° C. to obtain an optical isomer α-maltose content of 66.2 w / w% and a water content of 0.55 w / w%
The crystalline α-maltose powder of was obtained in a yield of about 94% based on high-purity maltose as a raw material.

This product, like the crystalline α-maltose powder obtained by the method of Reference Example 1, can be advantageously used as a dehydrating agent for various hydrous substances.

Reference Example 3 A commercially available bacterial liquefying α-amylase was added to a suspension of 2 parts by weight of corn starch and 10 parts by weight of water, gelatinized by heating to 90 ° C, and then heated to 130 ° C to stop the enzyme reaction, A liquefied solution of DE about 2 was prepared, and this liquefied starch solution was rapidly cooled to 55 ° C and then Pseudomonas amyloderamosa ATC
Isoamylase (EC3.2.1.
68) was added to 120 units per starch roof tile and 30 units of β-amylase derived from soybean, and saccharification was carried out for 36 hours while maintaining the pH at 5.0, followed by purification in the same manner as in Reference Example 1 to obtain a maltose content of 88.6.
A w / w% high-purity maltose solution was obtained, and then concentrated under reduced pressure to obtain a syrup having a water content of 3.5 w / w%.

Then, the mixture was transferred to an auxiliary crystallizer, to which the crystalline α-maltose obtained by the method of Reference Example 2 was added in an amount of 2.5 w / w% per syrup solid, and the mixture was agitated for 10 minutes at 120 ° C. It was taken out in a vat, crystallized and aged at 70 ° C. for 18 hours, and thereafter pulverized and dried in the same manner as in Reference Example 1 to obtain a crystalline product having an optical isomer α-maltose content of 63.9 w / w% and a water content of 0.60 w / w%. The α-maltose powder was obtained in a yield of about 94% based on the raw material of high-purity maltose.

This product, like the crystalline α-maltose powder obtained by the method of Reference Example 1, can be advantageously used as a dehydrating agent for various hydrous substances.

Reference Example 4 A starch sugar solution having a maltose content of 79.6% (manufactured by Hayashibara Co., Ltd., trade name: HM-75) was made into a 45 w / w% aqueous solution to give a raw sugar solution. The fractionation resin is an alkali metal type strongly acidic cation exchange resin (trade name XT-10 manufactured by Tokyo Organic Chemical Industry Co., Ltd.
22E, Na ⁺ type) was used to fill a jacketed stainless steel column with an inner diameter of 5.4 cm in the form of an aqueous suspension. At this time, four columns each having a resin layer length of 5 m were packed, and the four columns were connected so that the liquid flowed in series to give a resin layer total length of 20 m.

While maintaining the temperature inside the column at 55 ° C, add 5 v / v% of the raw sugar solution to the resin, and then warm water at 55 ° C was flowed at a flow rate of SV 0.13 to fractionate the fraction with a high maltose content. A high-purity maltose solution having a maltose content of solid matter of 94.4 w / w% was obtained.

The high-purity maltose solution collected by performing the above-mentioned fractionation treatment 20 times was concentrated under reduced pressure to give a syrup having a water content of 4.0 w / w%, which was transferred to an auxiliary crystallizer and the crystalline α-maltose obtained by the method of Reference Example 2 was obtained. Was added to the syrup solid matter at 2.0 w / w%, and the mixture was crystallized with stirring at 110 ° C for 20 minutes. Then, it was processed into a granular powder by a screw type extrusion granulator, transferred to a drying chamber and dried with hot air at 80 ° C for 2 hours. Crystallized and aged to obtain crystalline α-maltose powder with optical isomer α-maltose content of 69.2w / w% and water content of 0.48w / w% in a yield of about 93% based on high-purity maltose as a raw material. It was

This product, like the crystalline α-maltose powder obtained by the method of Reference Example 1, can be advantageously used as a dehydrating agent for various hydrous substances.

Examples of the present invention and excellent effects will be described below.

Example 1 4 kg of Soboro-style fertilizer glutinous flour was dissolved in water 6 and poured into a wooden frame covered with a wet cloth, steamed at 100 ° C. for 20 minutes, and then the crystals obtained by the method of Reference Example 1 Α-maltose powder 8Kg
And knead 1 kg of sugar, then add 1 kg of starch syrup, knead thoroughly and mold, and then leave it in the room for 16 hours to convert crystalline α-maltose into β-maltose hydrous crystals in the surface layer of this product. It was converted and lightly rolled to crack the surface, yielding soybean-like fertilizer.

This product had a good flavor, was not susceptible to microbial contamination, and maintained high quality for a long time. This product has good digestion and absorption, and is suitable as a nutritional supplement after illness.

Example 2 Powdered egg yolk 60-
Sterilized at 64 ° C., and mixed with 1 part by weight of the obtained liquid egg yolk at a ratio of 4 parts by weight of the crystalline α-maltose powder obtained by the method of Reference Example 4, transferred to a vat and left for 2 days. β
-Converted to maltose hydrous crystals to prepare blocks.

This block was pulverized with a cutting machine and classified to obtain powdered yolk.

The product can be advantageously used as a nutrient for oral liquid foods, tube liquid foods, and the like.

Further, it can be advantageously used as a skin beautifying agent, a hair-growth agent and the like.

The case where this product is used as a nutrient for a solid preparation for liquid food is as follows.

500 parts by weight of crystalline α-maltose obtained by the method of Reference Example 1, 270 parts by weight of powdered egg yolk obtained in this example, 209 parts by weight of skim milk powder, 4.4 parts by weight of sodium chloride, 1.85 parts by weight of potassium chloride, sulfuric acid Magnesium 4 parts by weight, thiamine 0.
01 parts by weight, sodium ascorbate 0.1 parts by weight, vitamin E acetate 0.6 parts by weight and nicotinic acid amide 0.04
It was possible to prepare a liquid edible solid preparation by preparing a formulation consisting of parts by weight, filling 25 g each of the formulation into a moisture-proof laminated pouch, and heat-sealing.

This solid formulation reduces moisture in the atmosphere in the sachet, does not require cold storage, and is stable at room temperature for a long time.

In addition, dispersion and dissolution in water are good.

This solid preparation is used by orally or by tube administration to the nasal cavity, stomach, intestine, etc. by dissolving one bag in about 150 to 300 ml of water to give a liquid food.

Example 3 Powdered medicinal liquor 10 g of pullulan was dissolved in medicinal liquor 2, and 10 Kg of crystalline α-maltose powder obtained by the method of Reference Example 3 was mixed, and then blocked and powdered in the same manner as in Example 2. Got powdered sake.

This product has a sufficient medicinal effect and is convenient to carry.

In addition, this powder is molded by a granule molding machine and a tableting machine,
It can also be advantageously used as a granule or a tablet.

Example 4 20 kg of crystalline α-maltose powder obtained by the method of Reference Example 2 was mixed with 10 kg of powdered butter butter with a mixer, and then blocked as in Example 2 and powdered to obtain powdered butter.

This product can be advantageously used as a therapeutic nutrient for oral liquid foods, tube liquid foods and the like.

Example 5 Crystalline α-obtained by the method of Reference Example 3 in 2 Kg of powder cream fresh cream
After mixing 8 kg of maltose powder, it was blocked and powdered in the same manner as in Example 2 to obtain a powder cream.

This product is a powdered cream with a good flavor and can be advantageously used as a therapeutic nutrient for oral liquid foods, tube liquid foods and the like.

Further, it can be advantageously used as a skin beautifying agent and a hair beautifying agent.

Example 6 Powdered yogurt 10 kg of crystalline α-maltose powder obtained by the method of Reference Example 4 was mixed with 2 kg of plain yogurt, and then blocked and powdered in the same manner as in Example 2 to obtain powdered yogurt.

This product not only has a good flavor, but can also stabilize lactic acid bacteria for a long period of time in a living state. Therefore, this product can be advantageously used as a live bacteria intestinal preparation and as a therapeutic nutritional agent such as oral liquid food, tube liquid food.

Further, the present powder can be advantageously molded by a granulating machine, a tableting machine or the like to give a lactic acid bacterium preparation, which can be used as an intestinal stabilizer.

Example 7 Powdered ginseng extract Powdered ginseng extract was prepared by kneading 500 g of ginseng extract with 1.5 kg of crystalline α-maltose powder obtained by the method of Reference Example 1 and then blocking and kneading in the same manner as in Example 2. Got

This product was granulated with a proper amount of Vitamin B ₁ and Vitamin B ₂ powder in a granulating machine to obtain a vitamin-containing granular ginseng extract.

This product can be advantageously used as a fatigue recovery agent, tonic, tonic agent, etc. It can also be used as a hair restorer.

Example 8 Solid preparation A newborn hamster is injected with an antiserum prepared by a known method from a rabbit to weaken the immune response of the hamster, and then BALL-1 cells are subcutaneously transplanted to the hamster, followed by a usual method. It was raised for 3 weeks. The subcutaneously formed tumor was excised, cut into small pieces, dispersed in physiological saline, and loosened. The obtained cells were washed with serum-free RPMI 1640 medium (pH 7.2), suspended in the same medium at about 2 × 10 ⁶ / ml, and kept at 35 ° C.
To this, partially purified human interferon was added at a rate of 200 U / ml and kept for about 2 hours, and then Sendai virus was added at a rate of about 300 hemagglutination / ml and kept for 20 hours to induce human interferon. It was This is about 4
Precipitate was removed by centrifugation at about 1,000 g at ℃, the obtained supernatant was further refined, and the solution was applied to an antibody column on which anti-interferon antibody was immobilized according to a known method, and After removing the adsorbed fraction, the adsorbed surface fraction is eluted and the membrane is concentrated to a concentration of about 0.01 w / v%, specific activity of about 1.5 x 10
⁸ U of concentrate was obtained in a yield of about 4 ml per hamster.

Pyrogen-free crystalline α obtained by the method of Reference Example 1
-Take 8g of maltose into 100ml moisture-proof plastic bottle, put 0.2ml (about 3 million U) of the interferon concentrate obtained in advance into this, and aseptically seal with a rubber stopper and cap to obtain a solid formulation. Obtained.

Since this production method is dehydrated by simply adding the interferon-containing liquid to crystalline α-maltose powder, it does not require treatment for freeze-drying, equipment, energy, etc., and is also effective for stabilizing interferon. Target.

Since this product is easily soluble in water, it can be used as a test reagent, antiviral agent, antitumor agent, etc.
It can be advantageously used as an injection for a vein or the like. In addition, the product can be advantageously used as an internal preparation, an oral preparation and the like.

The activity of human interferon was measured by a known plaque half method using FL cells. The hemagglutination value is
JESalk "The Journal of Immunology Vol.49" 87-
It measured according to the method of page 98 (1944).

Example 9 Solid Formulation A newborn hamster was injected with an antiserum prepared by a known method from a rabbit to weaken the immune response of the hamster, and then
Subcutaneously, human-derived mononuclear cells that had been cultured and established by culture with the SV-40 virus were transplanted, and after breeding for one week by the usual method, 10 ⁷ live cells of BCG were intraperitoneally injected. , And further raised for 2 weeks. About 15 g of the tumor that was subcutaneously excised was excised, cut into small pieces, and then suspended in trypsin-containing physiological saline to disperse and separate the cells. This cell contains human serum 5 v / v% pH 7.2
Washed with Eagle's minimal basic medium and diluted to a medium of the same composition kept at 37 ° C to a cell concentration of about 5 × 10 ⁶ × ml,
E. coli-derived endotoxin was added to this at a rate of about 10 μg / ml, and the mixture was kept for 16 hours to induce the Tumor necrosis factor.

This was centrifuged at 4 ° C. and about 1,000 g to remove the precipitate,
The resulting supernatant was dialyzed for 21 hours against physiological saline containing 0.01M phosphate buffer at pH 7.2, and the precision solution was concentrated and freeze-dried to obtain a powder containing Tzumo necrosis factor activity. It was The obtained powder was reported by G. Bodo (Sympos
ium on preparation, standadization and clinical us
e of interferon, 11th International Immunobiologic
al Symposium 8 & 9 June 1977, Zagreb, Yugoslavi
Interferon is removed by means of adsorption / desorption on ion exchanger, molecular weight fractionation by gel filtration, concentration, and precision filtration according to a), further purified by ammonium sulfate salting out, Con A-Sepharose affinity chromatography, and concentrated. A sarcoma Hemorrhagic necrotic activity and high-purity Tumor necrosis factor concentration characterized by having no adverse effect on normal cells Approx. 0.01 w / v%
About 30 ml was obtained from the hamster as a concentrate. The Tumor necrosis factor thus obtained was a glycoprotein having a specific activity of about 3.5 × 10 ⁵ U without mixing of the inducer used.

Pyrogen-free crystalline α obtained by the method of Reference Example 4
-Maltose (50 g each) is placed in a 600 ml glass bottle, and 0.5 ml (approximately 1.75 × 10 ³ U) of the Tumor Necrosis Factor Concentrated Solution obtained previously is added to each, and the rubber stopper and cap seal are aseptically added. To obtain a solid preparation.

In the present production method, since the liquid containing the Tumor necrosis factor is dehydrated to the crystalline α-maltose powder, the treatment such as freeze-drying is not necessary, and the stabilization of the Tumor necrosis factor is also effective.

Since the product is easily soluble in water, it can be advantageously used as an antitumor agent, a nutritional supplement, etc. as an injection for infusion. In addition, the product can be advantageously used as an internal preparation, an oral preparation and the like.

The activity of Tumor necrosis factor was
ck Tumor Necrosis Factor in “Lymphokines” Vol.
II, pp235-272, Academic press (1981), Tsmore Necrosis Factor Sensitivity L-929
A known method for measuring the number of surviving cells after culturing for a certain period of time using cells was used.

Example 10 Ointment plaster for treating wounds Crystalline α-maltose 500 g obtained by the method of Reference Example 3
50 ml of methanol in which 3 g of iodine was dissolved was added and mixed,
Further, 200 ml of 10 w / w% pullulan aqueous solution was added and mixed, and allowed to stand overnight at room temperature to be converted into β-maltose hydrous crystals,
A plaster for treating a wound, which has a proper extension and shows adhesiveness, was obtained.

This product can be used for treating wounds such as cuts, abrasions, burns, and ulcers caused by athlete's foot by directly applying it on the wound surface or by applying it on gauze, oil paper and the like.

In addition, since this product acts not only as a bactericidal action by iodine but also as a nutrient supplement for cells by maltose, the healing period is shortened and the wound surface is healed neatly.

(Effect of the invention) As is clear from the above, the crystalline α-of the present invention is
Maltose is a medicine such as a nutritional supplement and a bioactive substance,
The method for producing a drug by including β-maltose hydrous crystals in the raw materials or processed intermediates thereof and dehydrating it does not require harsh conditions such as heating and drying, so that decomposition of the active ingredient and activity A stable and high-quality pharmaceutical product can be easily produced without causing deterioration such as deterioration.

The dehydrated pharmaceutical product thus obtained can prevent microbial contamination, prevent deterioration by deterioration such as hydrolysis, rancidity, and browning, and can stably maintain the life of the product for a long period of time.

[Brief description of drawings]

FIG. 1 shows an X-ray diffraction pattern of an amorphous powder having an α-maltose content of 48.0 w / w%. FIG. 2 shows an X-ray diffraction pattern of a crystalline powder having an α-maltose content of 55.6 w / w%. FIG. 3 shows an X-ray diffraction pattern of a crystalline powder having an α-maltose content of 61.4 w / w%. FIG. 4 shows an X-ray diffraction pattern of a crystalline powder having an α-maltose content of 68.7 w / w%. FIG. 5 shows an X-ray diffraction pattern of a crystalline powder having an α-maltose content of 74.2 w / w%. Figure 6 shows β-maltose hydrous crystals (maltose HHH)
The X-ray diffraction pattern of the powder is shown.

Continuation of front page (51) Int.Cl. ⁵ Identification code Office reference number FI Technical display location B01J 20/22 Z 7202-4G C07H 3/04

Claims (16)

[Claims] 1. Crystalline α-maltose is added to a hydrous material selected from hydrous pharmaceuticals, hydrous raw materials and hydrous intermediates, and crystalline α-maltose is allowed to capture water of the hydrous substance for dehydration and crystallization. A dehydrated drug in which the crystalline α-maltose is converted into a β-maltose hydrous crystal and contained therein. 2. Crystalline α-maltose is an optical isomer α-maltose.
The dehydrated medicine according to claim (1), which contains 55% w / w or more of maltose. 3. Crystalline α-maltose is 85 w / solid per solid.
The dehydrated medicine according to claim (1) or (2), which is crystallized from high-purity maltose containing w% or more of maltose. 4. The crystalline α-maltose is a powder, and claims (1), (2) or
The dehydrated drug according to item (3). 5. The crystalline α-maltose having a water content of less than 3 w / w%, claims (1) and (2).
The dehydrated drug according to item (3) or (4). 6. The dehydrated drug contains gelatinized starch, alcohol, an oil-soluble substance or a physiologically active substance, as claimed in claims (1), (2) and (). Item 3), Section
The dehydrated medicine according to item (4) or (5). 7. The physiologically active substance is a lymphokine, a hormone, or an extract, wherein
The dehydrated drug according to item (6). 8. The dehydrated medicine is used orally or parenterally, and claims (1) and (1) are included.
(2), (3), (4), (5), (6) or
The dehydrated drug according to item (7). 9. A crystalline alpha-maltose is added to a hydrous material selected from hydrous pharmaceuticals, hydrous raw materials and hydrous processed intermediates to capture water in the crystalline alpha-maltose for dehydration. At the same time, the method for producing a dehydrated medicine is characterized in that crystalline α-maltose is converted into β-maltose hydrated crystals and the crystals are contained. 10. Crystalline α-maltose is an optical isomer α
-The method for producing a dehydrated pharmaceutical product according to claim (9), which contains 55 w / w% or more of maltose. 11. Crystalline α-maltose is 85 per solid.
The method for producing a dehydrated medicine according to claim (9) or (10), which is characterized by being crystallized from high-purity maltose containing w / w% or more of maltose. 12. The method for producing a dehydrated medicine according to claim (9), (10) or (11), wherein the crystalline α-maltose is a powder. 13. The crystalline α-maltose having a water content of less than 3 w / w%, claims (9) and (9).
The method for producing a dehydrated medicine according to item (10), (11) or (12). 14. The dehydrated medicine is gelatinized starch, alcohol,
Claims characterized by containing an oil-soluble substance or a physiologically active substance (9), (10), (11)
The method for producing a dehydrated pharmaceutical according to item (12) or (13). 15. The dehydrated medicine according to claim 14, wherein the physiologically active substance is a lymphokine, a hormone or an extract. 16. The dehydrated medicine is used orally or parenterally, and (9),
The method for producing a dehydrated medicine according to item (10), item (11), item (12), item (13), item (14) or item (15).