JPS62126118A - Dehydrated medicine and production thereof - Google Patents

Abstract

PURPOSE:To obtain a stable dehydrated medicine without causing deterioration in quality, by incorporating crystalline alpha-maltose in a hydrous material, e.g. hydrous nutrient material or hydrous physiologically active material, etc., and converting the crystalline alpha-maltose into hydrous beta-maltose crystals. CONSTITUTION:A dehydrated medicine obtained by incorporating crystalline alpha-maltose in a medicine, raw material therefor or processing intermediate thereof to convert the alpha-maltose into hydrous beta-maltose crystals and reducing the moisture of a hydrous material, e.g. the above-mentioned medicine. Crystalline alpha-maltose, obtained by concentrating an aqueous solution of high-purity maltose with >=85wt%, based on the solid, maltose content under reduced pressure to give a syrup with <10wt% moisture content in a high concentration and crystallizing the above-mentioned syrup in the presence of a seed crystal while keeping at 50-130 deg.C and containing >=55wt% optical isomer alpha-maltose and <3wt% moisture content is preferred for the crystalline alpha-maltose.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a dehydration drug for improving health, treating injuries and diseases, promoting recovery, etc., and a method for producing the same.

More specifically, a dehydrated drug in which a pharmaceutical product, its raw material or a processing intermediate contains crystalline α-maltose and is converted into a β-maltose hydrate crystal, and a pharmaceutical product, its raw material or a processing intermediate product containing crystalline α- The present invention relates to a method for producing a dehydrated pharmaceutical, which comprises containing maltose and converting it into hydrated β-maltose crystals.

(General technology) Traditionally, for the purpose of improving health, treating injuries and diseases, promoting recovery, etc.
Various pharmaceuticals are used, including nutritional supplements, physiologically active substance agents, and bactericides.

In general, the water contained in nutritional supplements has a great effect not only on their physical properties but also on their shelf life. Water-containing nutrients are susceptible to microbial contamination, and furthermore, hydrolysis, rancidity,
It is easily susceptible to deterioration such as browning.

Typically, to extend the shelf life of hydrous nutrients, e.g.
Various dehydration methods are used, including sugar pickling, salt pickling, and drying.

However, sugar is too sweet to suit modern tastes, is a major inducer of tooth decay, and has other drawbacks such as increasing blood cholesterol when ingested in large amounts. .

It has also been pointed out that excessive intake of salt is a major cause of adult diseases such as high blood pressure and cancer, and people are advised to reduce their intake as much as possible.

Furthermore, with the drying method, quality deterioration is unavoidable during the process, and currently only nutrients with poor flavor can be obtained.

For example, in the case of physiologically active substances containing lymphokines, hormones, vitamins, probiotics, enzymes, antibiotics, etc., they are unstable in the presence of high moisture;
Usually, in order to improve its stability, products are produced by drying methods such as heat drying and vacuum drying in the presence of a large amount of stabilizers.

Albumin, which is used as a stabilizer,
There are water-soluble polymer compounds such as casein, gelatin, and hydroxyethyl starch.

However, drying in the coexistence of stabilizers such as water-soluble polymer compounds is extremely difficult and not only wastes a large amount of energy, but also causes the resulting dried product to become poorly water-soluble and reduce the activity of physiologically active substances. There is a danger that it may cause

(Problems to be Solved by the Invention) The present inventors focused on maltose with the aim of solving the drawbacks of conventional dehydration methods for pharmaceuticals for promoting health, treating injuries and diseases, promoting recovery, etc. We conducted intensive research on its use.

As a result, we found that crystalline α-maltose acts as a powerful dehydrating agent by incorporating crystalline α-maltose into hydrated substances such as hydrated nutrients and hydrated physiologically active substances and converting it into hydrated β-maltose crystals. The present invention was completed by confirming that stable pharmaceuticals can be easily produced without deterioration of quality.

The present invention focuses on crystalline α-maltose, which has not received any attention as a dehydrating agent in the past.
- The present invention provides a method for dehydrating hydrated materials by containing maltose as a dehydrating agent.

The method of dehydrating hydrated materials according to the present invention is preferable as a method for dehydrating materials that contain water gold, especially those that contain free water different from bound water such as crystallized water, such as dry nutritional supplements, etc. In addition, when reducing the moisture contained in the atmosphere inside a moisture-proof container containing
It can be advantageously applied to reduce the moisture content of various hydrated materials such as pharmaceuticals such as nutritional supplements, physiologically active substances, and bactericides, their raw materials, and processing intermediates.

When these hydrated substances contain crystalline α-maltose, the crystalline α-maltose strongly takes up about 5 g of water by weight from the hydrated substances as β-maltose-containing ice-crystalline water. It has been found to substantially reduce and dehydrate water.

For example, in a moisture-proof container containing a dry nutritional supplement such as a solid preparation for liquid food, crystalline α
- It has been found that by allowing maltose to coexist, the relative humidity inside the container can be extremely reduced and high quality and stable quality can be maintained for a long period of time.

At this time, crystalline α-maltose traps water and becomes β-maltose.
Even during and after conversion into maltose-containing ice crystals, it does not become sticky or run off, so there is no need to worry about contaminating dry nutrients or moisture-proof containers.

Moreover, maltose itself is a non-toxic, harmless natural sweetener and poses no danger.

For example, in the case of high moisture nutrients such as liquids and pastes such as fresh cream and egg yolks, crystalline α-maltose is added to convert β-maltose into hydrated ice crystals. High-quality dehydrated nutritional supplements with reduced moisture content, for example, nutritional supplements in the form of maskit or powder, can be produced very easily. Since this method does not require harsh conditions such as heating and drying, it has the feature that liquid or paste high-moisture nutrients can be easily converted into dehydrated nutrients without deterioration.

In addition, 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, etc., to obtain crystalline α-maltose.
To obtain a dehydrated nutrient in which maltose is partially converted into β-maltose-containing hydrated ice crystals, in other words, both β-maltose-containing hydrated ice crystals contain crystalline α-maltose,
When this is sealed in a moisture-proof container, the moisture in the atmosphere inside the container is captured and dehydrated by crystalline α-maltose as β-maltose-containing ice crystal water, and the relative humidity is extremely reduced. It has been found that it can be kept dry.

As a result, the dehydrated nutritional supplement obtained by the method of the present invention is
It was found that it not only prevents microbial contamination, but also prevents deterioration such as hydrolysis, rancidity, and browning, thereby stably maintaining high-quality products with good flavor over a long period of time.

Furthermore, in the case of pasty physiologically active substances such as aqueous solutions of lymphokines and antibiotics, medicinal ginseng extracts, and stupa extracts, crystalline α-maltose can be added to these to convert them into β-maltose-containing hydrated ice crystals.
High-quality dehydrated physiologically active substance preparations with substantially reduced water content, for example, physiologically active substance preparations in the form of maskite or powder, can be produced very easily.

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

In addition, there is no need to worry about wasting energy for drying stabilizers such as water-soluble polymer compounds.
By appropriately using it as needed, it is also possible to advantageously produce a higher quality and stable dehydrated physiologically active substance agent.

Alternatively, for example, a certain amount of crystalline α-maltose is taken into a vial, and an aqueous solution containing a physiologically active substance such as lymphokine or hormone is added to the crystalline α-maltose.
- It is also advantageous to add an amount of water smaller than the amount of water required for converting maltose into β-maltose hydrated ice crystals and seal the container tightly to produce a solid preparation for injection.

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

As a result, the dehydrated pharmaceutical obtained by the present invention not only has an easy manufacturing process, but also has characteristics such as being able to stably maintain its high quality over a long period of time, and furthermore, quickly dissolving in water when used. It was also found that it has

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

Prior to the present invention, the present inventors conducted research on methods for producing crystalline α-maltose, particularly crystalline α-maltose powder.

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

High-purity maltose as a raw material may be obtained by using commercially available β-maltose hydrated ice crystals or by saccharifying starch according to a conventional method.

Methods for preparing high-purity maltose from starch include, for example, Japanese Patent Publication No. 11437/1983, Japanese Patent Publication No. 56-1
85 per solid product produced by applying β-amylase to gelatinized or liquefied starch as disclosed in Publication No. 7078 etc.
Any high-purity maltose with a W/W% or higher purity can be used, for example, even if it is commercially available β-maltose hydrated ice crystals or one prepared by saccharifying starch according to a conventional method. Work.

Methods for preparing high-purity maltose from starch include, for example, Japanese Patent Publication No. 11437/1983, Japanese Patent Publication No. 56-1
The method disclosed in Japanese Patent No. 7078, etc., in which β-amylase gold is applied to gelatinized or liquefied starch, the resulting maltose is separated from polymer dextrin, and high-purity maltose gold is collected, or, for example, Japanese Patent Publication No. 13089-1989 There is a method of collecting all high-purity maltose by allowing starch cutting enzymes such as in-amylase and pullulanase and β-amylase to act on gelatinized or liquefied starch, as disclosed in Japanese Patent Publication No. 54-3938. .

Furthermore, contaminant sugars such as maltotriose contained in high-purity maltose obtained by these methods are disclosed in, for example, Japanese Patent Publication No. 56-28153, Japanese Patent Publication No. 57-3356, Japanese Patent Publication No. 56-28154, etc. All the enzymes that have been used are activated to produce maltose, and furthermore,
For example, it is possible to completely increase the purity of rainbow maltose by removing all contaminant sugars using a column fractionation method using a salt-type strongly acidic cation exchange resin as disclosed in JP-A No. 58-23799. It's convenient. Furthermore, this fractionation method can be used regardless of whether it is a fixed bed method, a moving bed method, or a pseudo moving bed method.

In order to produce crystalline α-maltose powder from high-purity maltose with a content of 85 w/w% or more based on the solid matter obtained in this way, for example, these high-purity maltose can be
A highly concentrated sillage of less than 0 w/w%, preferably 2.OW/W% or more and less than 9.5w/w%, and this sillage is maintained at a temperature range of 50°C to 130°C in the coexistence of seed crystals. It can be produced by crystallizing α-maltose.

Crystalline α-maltose has a water content of Low/w% or more,
Substantially no crystallization, especially when the water content is 12 w/w % or more 25
It has been found that if the concentration is less than W/W%, not only the crystalline α-maltose in the seed crystals tends to dissolve and disappear, but also the β-maltose-containing ice crystals are more likely to crystallize. Also, water 2
．． It has been found that the crystallization of crystalline α-maltose from high-concentration cilantro (less than Qw/w%) is relatively slow.

Furthermore, the temperature G during crystallization is preferably in the range of 50°C to 130°C, and preferably in the range (11)'O to 120°C. At a temperature below 50°C, crystalline α-maldose It was found that the crystallization was extremely slow and unsuitable for industrial implementation.

Furthermore, at temperatures exceeding 130 DEG C., not only is crystallization slow, but also the coloring during crystallization is significant, making it unsuitable as a method for producing crystalline α-maltose powder.

Therefore, in order to crystallize crystalline α-maltose, highly concentrated maltose with a moisture content of less than 10 w/w% is crystallized while maintaining the temperature range of 50°C to 130°C in the coexistence of seed crystals. That is essential. At this time, the method of converting high-purity maltose into a high-concentration syrup with a moisture content of less than IQw/w% is, for example, a method in which the maltose content is F) 85
Commercially available β-maltose hydrated ice crystals with a water content of W/W% or more may be heated and dissolved in a small amount of water to form a high-concentration syrup with a water content of less than 10w/w%. A high-purity maltose aqueous solution with a solid content of 85 w/w% or more is concentrated under reduced pressure to reduce the water content to lQ w/w%.
It can also be used as a high-concentration syrup with a water content of less than 35%.
Spray drying an aqueous solution less than 1 w/w:
It may also be a high concentration Shirabu droplet of less than 0 w/w%.

Next, to crystallize α-maltose in the presence of seed crystals, it is usually 0.001 w/w or more of 100 W for a high-concentration solid substance of high-purity maltose.
/W%, preferably 0.1w/w% or more 20w/
It is sufficient if crystalline α-maltose can be crystallized by coexisting less than w% of crystalline α-maltose seed crystals.
Crystallize by mixing seed crystals with a high-concentration silica lubrication of less than /w%, or mix seed crystals with silica lubrication of high-purity maltose with a moisture content of 1 ow/w % or more and less than 20 w/w 1. While the maltose does not dissolve or disappear, use a spray drying method or the like to crystallize it into high-concentration droplets with a water content of less than IQ w/w%, or further reduce the water content of high-purity maltose to IQ w/w.
% or more and less than 35 w/w% to form droplets with a rainbow moisture content of less than 10 w/w% by a spray drying method, and a method such as bringing seed crystals into contact with the droplets to crystallize them can be selected as appropriate.

However, 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 Kq/cfI or more during crystallization and auxiliary crystallization of crystalline α-maltose. Therefore, a method for producing crystalline α-maltose powder using, for example, an extrusion granulator, which requires pressure and compression, can be advantageously carried out.

For your information, it has been found that it is possible to advantageously promote the crystallization without drying the maskilla during crystallization (1-1). Drying methods include normal pressure, reduced pressure, or increased pressure;
A stationary state, a flowing state, etc. can be selected as appropriate.

These methods for completely promoting the crystallization of crystalline α-maltose are carried out when the optical isomer α-maltose content of the present invention is 55w/
It is possible to shorten the time required to reach a total concentration of more than 215 w%, which not only increases the production efficiency of crystalline α-maltose powder, but also extremely reduces the degree of coloration of crystalline α-maltose powder. This method is advantageous as a method for producing high-quality crystalline α-maltose powder in large quantities.

Alternatively, a combination of two or more of these methods may be used, for example, the optical isomer
- A mass kit with a maltose content of more than 48 w/w % is then formed into various shapes such as powder, strands, blocks, etc., and further aged while crystallizing and drying while maintaining a temperature range of 50°C to 130°C. Optical isomer α
- A process for producing a total crystalline α-maltose powder with a maltose content of 55% w/w or more can also be carried out with great advantage.

In addition, the ripening conditions are usually about 0.1 to 24 hours in the temperature range of 50°C to 100°C, about 0.5 to 18 hours in the temperature range of 130°C over 100°C; It has been found that when subjected to harsh conditions for a long period of time, the degree of coloration of the obtained crystalline α-maltose powder increases and its commercial value is impaired.

Crystallization while machining/drying under pressure during ripening promotes the crystallization of crystalline α-maltose and can significantly shorten the ripening time.
This is convenient as a method for producing maltose powder in large quantities.

Methods for producing crystalline α-maltose powder having an optical isomer α-maltose content of 55 w/w or more include, for example, extrusion granulation method, block pulverization method, spray drying method, fluidized granulation method, etc. There is.

In the case of the extrusion granulation method, for example, high-concentration silica granules with a water content of less than 10 w/w of high-purity maltose are added at a total temperature of 50°C.
While maintaining the temperature range from 130℃ to 130℃, crystalline α
- Knead maltose seed crystals and form auxiliary crystals to form optical isomer α-
A granular massite or granular powder obtained by using a massite with a maltose content exceeding 43 w/w% is subjected to a total extrusion granulator, and the resulting massite is crystallized and aged without drying while maintaining the temperature range from 50°C to 130°C. and optical isomer α-
Crystalline α-maltose powder having a maltose content of 55 w/w% or more is collected.

High-concentration maltose with a moisture content of less than IQ w/w% is extruded into an extrusion granulator without the coexistence of seed crystals, and the resulting high-concentration gang droplets have crystallinity α.
- Contact with maltose seed crystals at 50°C to 130°C
While maintaining the temperature range, crystallization and ripening without drying,
It is also possible to collect the entire crystalline α-maltose powder having an optical isomer α-maltose content of 55 w/w% or more.

In the case of the block crushing method, for example, high-purity maltose with a moisture content of less than 10 w/w% is added to a high-concentration silane crystal auxiliary crystal while maintaining a temperature range of 9.50°C to 130°C. -Mix all the maltose seed crystals and auxiliary crystals to obtain a mass kit with a content of the optical isomer α-maltose exceeding 4+3 W/W%, take it out into an aluminum vat, for example, and heat it at a temperature of 50°C to 130°C. Crystallization and solidification are carried out while maintaining the crystallization within the range, and the entire block obtained is pulverized with a cutting machine, hammer mill, etc., dried, and sieved to obtain the optical isomer α-
Crystalline α-maltose powder having a maltose content of 55% v/w or more is collected.

In the case of the spray drying method, for example, seed crystals of crystalline α-maltose are mixed with a sill of high-purity maltose with a water content of Low/W% or more and less than 20W/W%, and the seed crystals are mixed to prevent the seed crystals from dissolving or disappearing. Spray dry as quickly as possible using a high-pressure nozzle method or rotating disk method to reduce moisture to 10 w/w.
W: The gangway droplet is less than 4, and the droplet is heated between 50°C and 13°C.
Crystalline α-maltose powder having an optical isomer α-maltose content of 55 w/w % or more is obtained by crystallizing and ripening without drying while maintaining the temperature in the 0° C. range.

In the case of the primary fluidized granulation method, for example, a slag of high purity maltose with a moisture content of 15 w/w% or more and less than 35 w/w% is directed toward seed crystals of crystalline α-maltose that have been fluidized in advance. Then, the sea urchin is spray-dried to form high-concentration gang droplets with a moisture content of less than IQw/w%, and this is crystallized and ripened without drying while maintaining the temperature range from 50°C to 130°C to obtain the optical isomer α-maltose. A crystalline α-malus powder having a content of 55 w/w% or more is collected.

Furthermore, it is also advantageous to continuously produce crystalline α-maltose by continuously supplying a portion of the crystalline α-maltose obtained as described above to the seed 4.

The crystalline α-maltose powder of the present invention, which is produced in this way and has an optical isomer α-maltose content of 55 w/w % or more, is an elegant white powder with low sweetness, and its water content is low, usually 3%. less than w/w%, preferably 2w
/w%, the fluidity is substantially fluid, although the fluidity varies somewhat depending on the shape and size of the powder particles, the content of the optical isomer α-maltose, etc.

In addition, its melting point is 121 ~
125°C is also much higher, above 130°C, especially about 140°C in the case of crystalline α-maltose powder with an optical isomer α-maltose content of (11)% w/w or more.
Even with the above, there is no concern about adhesion or caking, and the powder is a crystalline powder with sufficient fluidity.

The crystalline α-maltose powder obtained in this way is
All of this, for example, when added to water-containing substances such as foods, pharmaceuticals, cosmetics, and industrial chemicals, the water contained in them is β-
It was discovered that maltose-containing ice crystals trap and fix crystal water and act as a strong dehydrating agent for water-containing substances.

Crystalline α-maltose is different from the conventional commercially available β-maltose containing hydrated ice crystals (Rinbara Co., Ltd., registered trademark Sunmalt), which can be used not only in water but also in organic acid aqueous solutions, salt aqueous solutions, protein aqueous solutions, emulsions, and alcohol. It has been found that it can be rapidly dissolved in various aqueous solutions such as aqueous solutions at high concentrations. This property is advantageous when using crystalline α-maltose as a dehydrating agent to produce various dehydrated metals with reduced water content from various hydrated materials.

The dehydrating agent of the present invention can be advantageously applied in cases where the entire atmosphere inside a moisture-proof container is to be completely moisture-proofed and dried, and in addition, in cases where the atmosphere inside a moisture-proof container is completely moisture-proofed, and when drying is being carried out, water-containing substances that are likely to undergo deterioration due to heat drying, vacuum drying, etc.
! In some cases, we manufacture high-quality dehydrated products in the form of maskit, powder, etc. from hydrated materials that are difficult to dry.

In particular, it can be advantageously used to dehydrate various hydrated materials such as organs, tissues, cells, ground products, extracts, components, or preparations thereof derived from animals, plants, and microorganisms.

For example, in the case of nutritional supplements, their raw materials or processed intermediates, natural products, juices, vegetable extracts, soy milk, nut paste, gelatinized starch paste and other agricultural products, raw eggs, lecithin,
Livestock products such as milk, fresh cream, yogurt, butter, and cheese; marine products such as sea urchin paste, oyster extract, and sardine paste; sweeteners such as maple syrup and honey; and alcoholic beverages such as sake, wine, and medicinal liquor; A stable and high quality dehydrated nutritional supplement can be easily produced from a paste-like product.

In addition, in the case of physiologically active substances, their raw materials, or processed intermediates, solutions containing lymphokines such as interferon, lymphotoxin, Tumor necrosis factor, macrophage migration inhibitory factor, colony stimulating factor, transfer factor, and interloquine, insulin, growth hormone, prolactin, erythropoietin,
Solutions containing hormones such as follicle-stimulating hormone, BCG vaccine, Japanese encephalitis vaccine, tetanus toxoid, Nobu antitoxin, biological products such as human immunoglobulin, penicillin, erythromycin, chloramphenicol, tetracycline, streptomycin, kanamycin sulfate, etc. Antibiotic-containing liquid, thiamin, riboflavin, ascorbic acid, cod liver oil, carotenoids, ergosterol,
Vitamin-containing liquids such as toco7z roll, enzyme-containing liquids such as lipase, elastase, urokinase, protease, β-amylase, isoamylase, glucanase, etc.
Extracts such as medicinal ginseng extract, stupa extract, and chlorella extract, as well as liquid and pasty materials such as lactic acid bacteria and yeast paste, are stable and high-quality dehydrated physiologically active substances without losing their active ingredients and activities. can be easily manufactured.

Furthermore, if the raw eggs, lecithin, fresh cream, honey, licorice extract, fragrances, colorants, enzymes, etc. are dehydrated, they can be advantageously used as high-quality skin beautifiers, hair beautifiers, hair growth agents, and the like.

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

As a method for incorporating crystalline α-maltose into a hydrous material, known methods such as mixing, kneading, dissolving, permeating, scattering, coating, spraying, and injecting may be used as appropriate until the desired dehydrated product is completed. selected.

The amount of crystalline α-maltose to be added to the hydrated material may vary depending on the amount of water contained in the hydrated material and the properties of the desired dehydrated product, but is usually 0.01 to 1 part by weight of the hydrated material. 500 parts by weight, preferably 0.1-100
Parts by weight. At this time, in order to further improve the quality of the obtained pharmaceutical product, it is possible to advantageously use appropriate flavoring agents, coloring agents, flavoring agents, stabilizers, and bulking agents ``he'' and ``he'' in combination.

In particular, regarding stabilizers, since the present invention uses a strong dehydration method using crystalline α-maltose, there is no need to limit the stabilizers to low-molecular compounds such as antioxidants, and it is not necessary to limit the stabilizers to low-molecular compounds such as antioxidants. High molecular compounds such as soluble starch, dextrin, cyclodextrin, flurane, ercinan, textran, xanthan gum, gum arabic, locust bean gum, guar gum, gum tragacanth, tamarind cum, carboxymethyl cellulose,
Substances such as hydroxyethyl cellulose, hydroxyethyl starch, pectin, agar, gelatin, albumin, casein and the like can also be advantageously utilized as stabilizers.

When using these water-soluble polymer compounds, for example,
By uniformly dissolving a water-soluble polymer compound in a liquid or pasty water-containing material in advance, and then uniformly containing crystalline α-maltose therein by mixing or kneading, fine β- A dehydrated article in which maltose hydrate crystals are precipitated is obtained. This product contains aroma components and active ingredients derived from water-containing substances that are either coated with a film of a water-soluble polymer compound or encapsulated in microcapsules surrounded by the film together with fine β-maltose water-containing crystals. ,
In addition, when cyclodextrino is used, all clathrate compounds are formed and their volatilization and quality deterioration are prevented, so it is extremely excellent in stably retaining aroma components and active ingredients derived from water-containing substances.

Various methods can be employed to produce the dehydrated article of the present invention, particularly the powdered article. For example, crystalline α-maltose is uniformly added to relatively high water content such as pharmaceuticals, their raw materials, or processing intermediates so that the moisture content is about 20 ψ or less, and then the product is placed in a vat or the like for about 1 to 10 minutes. 1
For 0 days, leave at about 10-50°C1, for example, at room temperature, and β-
It may be converted into maltose hydrate crystals, solidified into, for example, a gel-like form, and then manufactured by cutting, pulverizing, or other methods. If necessary, a drying process, a classification process, etc. can be added after the powdering process such as cutting and pulverization.

Further, a powder product can also be directly produced by a spraying method or the like. For example, while fluidizing crystalline α-maltose powder, a predetermined amount of liquid or paste water-containing material is sprayed onto the powder and brought into contact with the powder to form granules, and then granulation is carried out.
1) After converting into β-maltose hydrate crystals by aging at °C for about 1 to 24 hours, or by mixing or kneading crystalline α-maltose into a liquid or paste-like hydrate,
A powder product that can be sprayed immediately or by starting the conversion into β-maltose hydrous crystals is similarly aged,
The method of producing a powder product by converting it into hydrated β-maltose crystals is suitable as a mass production method.

In the case of this spraying method, the β-
Crystallinity α to promote conversion to maltose hydrated crystals
- What is the ripening period when β-maltose hydrated crystal seeds coexist with an amount of 1.0.01 to 1° w/w relative to maltose? If you use a short stick, you can use it to your advantage.

The powdered dehydrated pharmaceutical product obtained in this way can be used as it is or, if necessary, in combination with enhancers, excipients, binders, stabilizers, etc., and further made into granules, tablets, and capsules. It can also be freely molded into any suitable shape such as a rod, plate, or cube.

In addition, an aqueous solution containing a core of pharmaceutical intermediates such as granules and uncoated tablets, and an approximately 70 to 95 w/w% aqueous solution of crystalline α-maltos, preferably an appropriate amount of a binder such as a water-soluble polymer. It can also be advantageously carried out to produce a sugar coating by coating the β-maltose and then converting it into hydrated β-maltose crystals and crystallizing them.

In addition, when crystalline α-maltose is added to a highly water-containing hydrate by mixing, kneading, or other methods, when the crystalline α-maltose is converted into β-maltose hydrated crystals and dehydrated, β
- Expands its volume as it converts into maltose hydrous crystals. When the expansion is significant, it reaches about 1.5 to 4.0 times. In this way, those that expand and solidify have lower hardness and are easier to powder than those that expand less.
It has the characteristics of less wear and tear on cutting machines, crushers, etc., and significant savings in power consumption.

Further, by utilizing this expansion phenomenon, dehydrated articles of various shapes can be manufactured. For example, a high moisture content containing crystalline α-maltose is placed in plastic containers of various shapes such as flowers, birds, fish, dolls, etc., and then kept for about 5 to 90 hours.
By leaving it at room temperature, expanding and solidifying it, dehydrated articles of various shapes can be obtained. If necessary, a volatile solvent such as alcohol,
It is also possible to contain a blowing agent that generates carbon dioxide gas or the like together with crystalline α-maltose and heat it slightly.

The dehydrated articles of various shapes obtained in this way can be advantageously used for medicines and the like where the shapes can be enjoyed.

Additionally, 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 also be advantageously used as a dehydrating agent for such gelatinized starch.

For example, in gelatinized starch such as Gyuhi, by converting crystalline α-maltose into sasse β-maltose ice-containing crystals, the water content can be substantially reduced and microbial contamination can be prevented. .

In addition, crystalline α-maltose is easily and uniformly mixed with gelatinized starch and acts as an anti-aging agent, significantly extending the product life of various processed nutrients containing gelatinized starch. be able to.

In addition, crystalline α-maltose, for example,
Unlike the maltose syrup powder disclosed in Publication No. 48198, it shows a high affinity for alcohol.

Due to this property, methanol, ethanol, butanol,
It can also be advantageously used as a dehydrating agent for water contained in alcohol or alcohol-soluble substances such as propylene glycol, glycerin, and polyethylene glycol. For example, dehydrated alcohol-containing substances such as medicinal liquors are dehydrated with crystalline α-maltose to advantageously produce dehydrated medicines in the form of muskits and powders that retain their active ingredients, aroma, etc. in the resulting β-maltose hydrated crystals. can do.

In addition, active ingredients such as iodine can be stabilized by mixing an alcoholic solution of iodine with crystalline α-maltose and adding an aqueous solution containing a water-soluble polymer to convert it into β-maltose hydrous crystals. It is also advantageous to produce a mask-like ointment that retains its properties and has appropriate viscosity, spreadability, and adhesion.

Furthermore, although crystalline α-maltose is a hydrophilic carbohydrate, it exhibits surprisingly large lipophilic properties.

Due to this property, crystalline α-maltose can be advantageously used as a dehydrating agent for water contained in oil-soluble substances.

Oil-soluble substances, such as soybean oil, rapeseed oil, spicy oil, sesame oil, safflower oil, palm oil, cocoa butter, beef tallow, liver fat, chicken oil, fish oil, hydrogenated oil, citrus essential oils, flower essential oils, spices Oil, oil-soluble spices such as peppermint oil, spearmint oil, kola nut extract, coffee extract, oil-soluble coloring agents such as beta-carotene, paprika pigment, annatto pigment, chlorophyll, cod liver oil, vitamin A1 vitamin B2 butyrate ester, vitamins E1 vitamins include 1 oil-soluble vitamins such as hitamine D, oil-soluble hormones such as estrogen, progesterone, androgen, and frostaglandin, and highly unsaturated fatty acids such as linoleic acid, linuric acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, etc. It can be advantageously used as a dehydrating agent that strongly captures the moisture contained in oxygen.

Oil-soluble substances dehydrated by crystalline α-maltose are
It is of high quality and is resistant to quality deterioration such as hydrolysis and spoilage.

It is also advantageous to impregnate and mix crystalline α-maltose with oil-soluble substances to produce powdered nutrients, powdered vitamins, physiologically active substances such as hormones, and the like.

In this case, crystalline α-maltose acts not only as a dehydrating agent but also as a stabilizer, holding agent, excipient, carrier, and the like.

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

As described above, the present invention was achieved by the discovery that crystalline α-maltose strongly dehydrates various water-containing substances. By using it as an agent, it can reduce the flavor and aroma of water-containing substances such as liquids and pastes.
High-quality nutritional supplements with reduced water content and their active ingredients and activities are not degraded or reduced without being volatilized.
Pharmaceutical products such as high-quality physiologically active substance agents with reduced moisture content can be advantageously produced.

In addition, crystalline α-maltose is not only suitable for the special cases mentioned above, but is also a natural sweetener that maltose originally has, and there are no concerns about inducing cavities or increasing blood cholesterol. Since it also has properties such as imparting color, shine, viscosity, and water retention, it can be advantageously used in the production of nutritional supplements for oral use.

Moreover, crystalline α-maltose is a nutritional substance that is originally metabolized by maltose.

When used parenterally as an injection, it becomes isotonic at twice the concentration compared to glucose, so it can provide calories at twice the concentration, eliminating the need for large amounts of calories during surgery, etc. It is suitable as a nutritional supplement.

Experiment 1. Comparison of raw material maltose The raw material maltose is shown in Table 1, and various starch sugar products manufactured by Yurinbara Co., Ltd. are used.

In the case of a plain product such as Marustar (trade name) or HM-75, the product was directly placed in an evaporator and boiled under reduced pressure to a moisture content of 4.5% w/w.

Product name Sunmalt, Maltose H, Malt-, x,
I (H, maltose) (HH & D (7) β-? /+
/ ) - In the case of powdered products such as hydrated crystals, dissolve them by heating in a small amount of water, then boil them in an evaporator under reduced pressure to a moisture content of 4.5 W/W%.

The high-concentration silica with a water content of 4.5 W/W'% thus obtained was transferred to a auxiliary crystallizer, and about 50 W/W' of high-purity goomaltose ice-containing crystals (maltose HHH) was added to this in advance.
V% crystalline α-maltose was collected by crystallization from a hot methanol solution, and 2 w/w% of it was added as a seed crystal, and the mixture was heated at 120°C for 20
Stir for 9 minutes, then take out into an aluminum vat and
Prepare blocks by aging at 0°C for 16 hours. Then,
Cool to room temperature and grind to obtain a powder product. C, C using these powder products.

Sweeley et al., J. Am., Che.
m, Soc,, Vol, 85°2497-2507
(1963) to determine the content of the optical isomer α-maltose in maltose.
ola et al., J. Am. Chem., 3
oc,.

According to the method described in Mo1.78.2514-2518 (1956), an X-ray diffraction apparatus (manufactured by Rigaku Denki Co., Ltd., trade name Geigerflex RAD-1
[B, using Cu Kα rays] Perform powder X-ray diffraction on the entire circumference to check for the presence of crystals. The results are shown in Table 1. Its X-ray diffraction patterns are shown in Figures 1 to 5. Figure 1 shows an amorphous powder with an α-maltose content of 43 w/w%, Figure 2 shows a crystalline powder with an α-maltose content of 55.6 w/w%, and Figure 3 shows an α-maltose-containing crystalline powder. Takashi (10). Figure 4 shows the α-maltose content of 4 w/w crystalline powder, which is 68.7.
Figure 5 is an X-ray diffraction pattern of a crystalline powder with an α-maltose content of 74.2% w/w. Note 1. As a control experiment, X-ray diffraction was performed on an amorphous powder of β-maltose hydrate crystals (maltose HHH) dissolved in total water by heating and dried under reduced pressure. The figure is obtained, and the raw material β
- In X-ray diffraction of maltose hydrated ice crystal maltose (HHH) powder, the X-ray diffraction pattern shown in Figure 6 was obtained.

It is clear from the results in Table 1: In the case of sea urchin, the precipitation of crystals was observed in X-ray diffraction, and the content of the optical isomer α-maltose was 55 W/W% or more, and the raw material maltose was , maltose content per solid matter, 985W
/W% or more was found to be necessary.

Experiment 2, Comparison of lipophilicity 2-1 Comparison of oil retention ability Prepared according to the method of Experiment 1 and the following test samples 1 to 8, sugar (Test A9), lactose (Tess) 410) T-particle size 4
A comparison was made with oil retaining duck as a powder of 5 to 150μ.

The oil holding power was measured in accordance with the method disclosed in JP-A-59-31650, in which 102 pieces of rapeseed oil were weighed into a beaker and powdered sugar was added while stirring.

This mixture has good fluidity when the amount of powdered sugar added is small, but as the amount increases, the mixture becomes more viscous and eventually forms a lump. If the amount added is further increased, the hardness will increase and eventually it will no longer hold together and will begin to separate.

With this point as the end point, the oil retention capacity was determined using the following formula.

The results are shown in Table 2.

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

To measure the emulsifying power, put 22 parts of soybean oil in a beaker, and add 2 parts of various sugar powders to this. Add everything and mix by stirring with a glass rod.

Place the resulting mixture in a test tube with a stopper, add 30 liters of water, shake gently by hand several times to mix, and leave to stand overnight at room temperature. The aqueous phase was observed with the naked eye to determine the intensity of the cloudiness.

In addition, when the emulsified aqueous phase was examined under a microscope, the presence of sugar crystal powder was not observed, and only a large number of oil droplets with a diameter of about 2 to 5 μm were observed. , the number of oil droplets is large.

The results are shown in Table 2.

Table 2 Nine.

It is clear from the results in Table 2 that crystalline α-maltose powder has excellent oil retention and emulsion properties, and is extremely lipophilic. It turned out that it has.

Experiment 3. Effect of high-purity maltose syrup water on crystallization of α-maltose Raw maltose is β-maltose hydrated crystal powder manufactured by Hayashibara Co., Ltd. Product name: Maltose HHH (maltose content 99.7 w/w %) The effect of high concentration of water in Shirub on the crystallization of crystalline α-maltose was investigated using f.

β-maltose hydrated ice crystal powder is heated and dissolved in a small amount of water,
Next, it was placed in an evaporator and boiled down under reduced pressure to prepare shirabu with various moisture contents. To this, seed crystals of crystalline α-maltose were added at 2w to 7w% based on the solid matter of shirafu, and the mixture was heated at 100°C.
The mixture was stirred for 5 minutes at 100° C. for auxiliary crystallization, then taken out into an aluminum vat, and aged at 70° C. for 6 hours to prepare a block. After cooling to room temperature, the total content of optical isomer α-maltose was measured.

The results are shown in Table 3.

Table 3 As is clear from the results in Table 3, crystalline α-maltose crystallizes when the moisture content of high-purity maltose is 10 v.
Less than t/w% is desirable, especially 'l, Qw/w
% or more and less than 9.5 w/w 1 was found to be suitable.

Experiment 4 Effect of temperature on the crystallization of crystalline α-maltose The raw material maltose was β-maltose-containing ice crystals manufactured by Hayashibara Co., Ltd. Product name: Maltose H (maltose content: 91
．． 5 w/w%) to investigate the effect on the crystallization of crystalline α-maltose.

β-maltose hydrated ice crystal powder is heated and dissolved in a small amount of water.
Next, put it in an evaporator and boil it under reduced pressure to reduce the moisture to 4.5w/
W% of Shirabu was prepared, 2 crystals of crystalline α-maltose were added to it at 2W/W% based on the solid matter of Shirabu, and 10
Auxiliary crystallization was carried out by stirring at 0°C for 5 minutes, then taken out into an aluminum vat, and crystallized and aged at temperatures ranging from 20°C to 140°C for 16 hours to prepare blocks. It was measured.

Furthermore, we measured the degree of coloration of these blocks. The degree of coloring is
420°C m in 10 wound cells in 30w/v% aqueous solution
and the absorbance difference at 720 nm (A4□.-7□.).

The results are shown in Table 4.

Table 4 As is clear from the results in Table 4, crystalline α-maltose is preferably crystallized at a temperature in the range of 50°C to 130°C, particularly preferably in the range of (11)°C to 120°C. It turns out that the ratio. However, the degree of coloration of crystalline α-maltose varies depending on the crystallization temperature, and is 130℃? It turns out that it increases significantly when you exceed it. That is, 140℃
It has been found that the degree of coloration of the crystallized product is about 14 to 20 times that at 100°C or lower, about 7 times that at 120°C, and about 3 times that at 130°C.

Experiment 5. Comparison of dehydration power of various sugars Anhydrous glucose, sugar, crystalline α-maltose prepared in Tests 1 and 5, and Mayu's raw material β-maltose hydrated ice crystals were used to prepare a powder with a particle size of approximately 100 to 150μ. They were placed in a plastic Petri dish with a diameter of 5 crn, and left in an atmosphere at 25°C with a relative humidity of 70°C.The water content (%) of these sugars was measured over time to determine the dehydration power. All strengths were compared.

The results are shown in Table 5.

As is clear from the results in Table 5, crystalline α-maltose has been found to act as a strong dehydrating agent until it captures approximately 5% w/w of its weight of water.

When we examined and compared the X-ray diffraction patterns of each sample over time, we found that there were no changes in anhydrous glucose, sugar, and hydrated β-maltose crystals. However, it has been found that crystalline α-maltose changes by trapping water and is converted into β-maltose hydrated crystals at about 5% water, reaching an equilibrium water content and becoming stable.

Mayu, in the same way, the same crystalline α-maltose was conditioned to a total relative humidity of 92% and placed in an atmosphere at 25°C, and its moisture content (%) was measured over time. Even after converting to maltose hydrated crystals, water is absorbed and the
It was found that the ratio reached equilibrium and stabilized at 8% moisture. In this case as well, the powder state is maintained and the wet flow is maintained:
,! l) No phenomena were observed.

Due to this property, crystalline α-maltose can be advantageously used as a dehydrating agent for pharmaceuticals such as nutritional supplements and physiologically active substance agents, raw materials thereof, and processing intermediates.

Experiment 6. Use of various sugars in sandwich cream Sand creams were prepared using various sugars, and their dehydration effects were compared.

The various sugars used were the same as those used in Experiment 5.

The preparation method is to take shortening 4257 in a mixer, add 500 f'ii of saccharide to it and mix, then add 252 f' of soybean oil (white squeezed oil) and 50 f of cocoa butter in advance.
Then, all of the melt was added and whipped to make a sandwich cream.

In addition, when all β-maltose hydrated crystals were used as the saccharide, it could not be mixed and a sand cream could not be produced.

The resulting sand cream was left in a harsh atmosphere at 29°C with a relative humidity of 92%, and its water content (%) decreased over time.
) and observe the condition of the sandwich cream.

The results are shown in Table 6.

Table 6 *The fat and oil have separated and become sticky.

※※ It is a stable and slightly hard sand cream with no separation of fats and oils.

As is clear from the results in Table 6, crystalline α-
Sand cream using maltose does not lose its shape,
It was found that the crystalline α-maltose used was converted into β-maltose hydrate crystals, which reached equilibrium with the atmospheric conditions and were stabilized.

Based on this fact, the prepared Tomo Sand Cream is stored in a moisture-proof container by sandwiching it between cookies, biscuits, etc. to capture moisture in the atmosphere and dehydrate it.
It has been found that not only can the relative humidity of the atmosphere be reduced, but also that the quality of the sand cream itself can be maintained stably for a long period of time without deteriorating its quality.

Experiment 7 Comparison of carbohydrates to gelatinized starch Dissolve 400 f of sticky rice flour in water (11)0 rnt.
Spread a wet cloth on the wooden frame and pour it into the wooden frame, all 10
Steam at 5°C for 10 minutes to obtain gelatinized starch.

This was mixed with the next crystalline α-maltose prepared in Test & 5 of Experiment 1 using a mixer containing the raw material β-maltose hydrated crystals, until it became homogeneous, and then 200 Pi of starch syrup was added. The mixture was then sufficiently kneaded to form the mixture, and was further lightly dried with warm air at 40°C for 2 hours to obtain a gyuhi.

When this product was left open in a room at 25°C, black mold colonies appeared after 12 days in the product using β-maltose hydrated crystals, but the product using crystalline α-maltose did not. No microbial contamination was observed even after 20 days.

In addition, after 20 days, we cut the whole sample and observed its entire cross section, and found that the surface layer of the sample using crystalline α-maltose was slightly hardened and crystals had precipitated, but the inside was as it was immediately after production. Similarly, it was translucent, had a moderate gloss, and had a high viscosity. Note that the surface layer crystals are crystalline α-
It was found that maltose was converted into β-maltose hydrated ice crystals.

On the other hand, the whole used β-maltose-containing ice crystal has mold on its surface, and the entire cross section is cloudy and lacks luster.

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 utilized in the production of pharmaceuticals containing gelatinized starch.

Hereinafter, a method for producing crystalline α-maltose powder will be described using a reference example.

Reference Example 1 Commercially available bacterial liquefied α-amylase was added to a suspension of 1 part by weight of potato starch and 10 parts by weight of water, and gelatinized by heating at 90°C.
Immediately heat the enzyme to 130°C to stop the enzyme reaction and reduce the DE to about 0.
A liquefied liquid of No. 5 was obtained. This starch liquefied liquid was rapidly cooled to 55°C and Pseudomonas amyloderasa (pseudomonas
as amyloderamosa) AT CC
In-amylase (EC
3,2,1゜68) Add 9100 units of starch tile and the same <50 units of soybean-derived β-amylase (EC3,2,1,2) (manufactured by Nagase Sangyo ■, trade name ≠ 1500). The mixture was saccharified for 40 hours while maintaining the pH at 5.0 to obtain a high purity maltose solution with a maltose content of 92.5 w/w% based on the solid matter, which was decolorized with activated carbon and desalted and purified with an ion exchange resin.

After concentrating this maltose solution to a concentration of 75%, it was placed in a auxiliary crystal can, and 11 powdered seed crystals of β-maltose monohydrate crystals were added to the temperature at 40°C, and slowly cooled while stirring.
It took two days to lower the temperature to 30℃, separate the honey using a basket centrifuge, and spray and wash all the crystals with a small amount of water to make them pure [99
, 0% high purity β-maltose hydrated ice crystals were obtained.

The high-purity maltose thus obtained was heated and dissolved in a small amount of water, then placed in an evaporator and boiled under reduced pressure to remove 5. ．． 5 w/w% of silica powder was then transferred to an auxiliary crystallizer, and xw/w% of crystalline α-maltose obtained by the method of test A6 was added thereto based on the solid substance of silica powder.
The mixture was stirred at 100°C for 5 minutes, then taken out into a plastic vat, and crystallized and aged at 70°C for 6 hours to prepare a block.

Next, the entire block was pulverized using a cutting machine and fluidized to dry, so that the content of the optical isomer α-maltose was 73.3 w/w.
'l = crystalline α-maltose powder is used as a raw material with high purity β
- A yield of about 92 w/w % based on maltose-containing ice crystals.

This product can be advantageously used as a dehydrating agent for hydrated products such as the pharmaceuticals of the present invention, their raw materials, or Karo-process intermediates.

Reference Example 2 The maltose content prepared by the method of Reference Example 1 is J
A high-purity maltose aqueous solution of 92.5 W/W% was concentrated under reduced pressure to a water content of 20 w/vr%, then sprayed from a nozzle with a high-pressure pump at the top of the spray drying tower, and dried with hot air at 100 ° C. On the moving wire mesh conveyor at the bottom of the drying tower,
The powder was dropped onto a fluidized crystalline α-maltose powder in advance, and was gradually moved to the outside of the drying tower while blowing warm air at 0°C under the conveyor, which took (11) minutes. The powder taken out was packed into an aging tower and crystallized and aged for 4 hours while blowing hot air at 70°C to obtain crystalline α-maltose with an optical isomer α-maltose content of 66.2 w/w%. Maltose powder was obtained at a yield of about 94% based on the high purity maltose used as the total raw material.

Similar to the crystalline α-maltose powder obtained by the method of Reference Example 1, this product can be advantageously used as a dehydrating agent for various hydrated substances.

Reference Example 3 Commercially available bacterial liquefied α-amylase was added to a suspension of 2 parts by weight of cornstarch and 10 parts by weight of water, heated to 90°C to gelatinize, and then heated to 130°C to stop the enzyme reaction. This starch liquefied liquid was rapidly cooled to 55°C to form a liquefied liquid with a DE of about 2.
s amyloderamosa) A TCC21
In-amylase (EC3,
2゜1.68) 120 units of t-starch, the same <30 units of soybean-derived β-amylase, and gold added, pH 5,
0 and saccharified for 36 hours, purified in the same manner as in Reference Example 1 to obtain a high-purity maltose solution with a maltose content of 88.6 w/w%, and then concentrated under reduced pressure to obtain a water content of 3.5 w/w%.
I made it as a syllabus.

Next, the crystalline α-maltose obtained by the method of Reference Example 2 was transferred to an auxiliary crystallizer, and 1) 2.5w of the crystalline α-maltose obtained by the method of Reference Example 2 was added to it
/w%, stirred at 120°C for 10 minutes, and then
It was taken out into an aluminum vat and crystallized and aged at 70°C for 18 hours, and then crushed and dried in the same manner as in Reference Example 1 to obtain crystalline α-maltose with an optical isomer α-maltose content of 63.9 W/W %. The powder was obtained in a yield of about 94-94% based on the raw material high-purity maltose.

Similar to the crystalline α-maltose powder obtained by the method of Reference Example 1, this product can be advantageously used as a dehydrating agent for hydrated substances.

Reference Example 4 A starch sugar solution with a maltose content of 79.6% (manufactured by Hayashibara Co., Ltd., trade name HM-75) was made into an aqueous solution with a total concentration of 45 w/w and made into a raw sugar solution. As the fractionation resin, an alkali metal type strongly acidic cation exchange resin (manufactured by Tokyo Organic Chemical Industry Co., Ltd., trade name XT-1022E, Na type) was used, and the inner diameter was 5.
A 4α jacketed stainless steel column was packed in the form of an aqueous suspension. At this time, four columns each having a resin layer length of 5 m were filled, and the four columns were connected so that the liquid flowed in series, resulting in a total resin layer length of 20 m.

While maintaining the same column temperature at 55°C, add 5 V/V% to the total resin of the raw sugar solution, and add 55°C warm water to it with SVo,
It was fractionated by flowing at a flow rate of 13, and the maltose-rich fraction was collected, and the maltose content was 94.4 W/W% per solid matter.
Obtain high purity maltose solution.

The high-purity maltose solution collected by performing the above fractionation process 20 times [--concentrated under reduced pressure to remove water content of 4. Qw/w% of silage was prepared, transferred to an auxiliary crystallizer, and obtained using the method of Reference Example 2. +2. Ow/w%
In addition, the mixture was stirred at 110°C for 20 minutes to produce auxiliary crystals, and then the screw was extruded into a granulator to form a granular powder, which was transferred to a drying room and dried with hot air at 80°C for 2 hours before being crystallized and aged to obtain the optical isomer α. - Crystalline α-maltose powder with a maltose content of 69.2% w/w was obtained in a yield of about 93% based on the raw material high purity maltose.

Similar to the crystalline α-maltose powder obtained by the method of Reference Example 1, this product can be advantageously used as a dehydrating agent for various hydrated substances.

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

Example 1 Soboro-style gyuhi mochi powder was dissolved in 4 kilograms of water and 6 tons of water, poured into a wooden frame covered with a wet cloth, steamed at 100°C for 20 minutes, and then added to it using the method of Reference Example 1 to make it particularly crystalline. Knead α-maltose powder 81'4 and sugar IKv, then add starch syrup IKq, knead thoroughly, and form the product.Furthermore, leave it indoors for 16 hours to form a crystalline α-maltose product in the coating layer.
- Maltose was converted into hydrated β-maltose crystals, which were lightly rolled to crack the surface to obtain a soboro-like gyuhi.

This product had a good flavor, was resistant to all microbial contamination, and maintained its high quality over a long period of time.

Example 2 Powdered egg yolk Egg yolk prepared from raw eggs was sterilized using a plate-type heat sterilizer (1
1) Sterilize at ~64°C, mix 1 part by weight of the obtained liquid egg yolk with 4 parts by weight of the crystalline α-maltose powder obtained by the method of Reference Example 4, transfer to a vat, A block was prepared by allowing β-maltose to be converted into water-containing ice crystals by standing for a day.

This block was pulverized by cutting and classified to obtain powdered egg yolk.

This product can be advantageously used as a nutritional supplement for oral liquid food, tubed liquid food, etc.

It can also be advantageously used as a skin beautifier, hair growth agent, etc.

Example 3 Powdered medicinal liquor Pullulan 102 was dissolved in 2 tons of medicated liquor, and Reference Example 3 was added to this.
After mixing 9 with the crystalline α-maltose powder 10 obtained by the method described above, it was blocked and powdered in the same manner as in Example 2 to obtain a powdered medicinal liquor.

This product has sufficient medicinal efficacy and is convenient to carry.

In addition, this powder is molded using a granulation machine and a tablet machine,
It can also be advantageously used in the form of granules and tablets.

Example 4 Crystalline α- obtained by the method of Reference Example 2 was added to 10 kg of powdered butter butter.
After mixing 20Kf of maltose powder with a mixer, it was formed into blocks and powdered in the same manner as in Example 2 to obtain powdered butter.

This product can be advantageously used as a therapeutic nutritional supplement such as oral liquid food and tubed liquid food.

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

This product is a powdered cream with a good flavor and can be advantageously used as a therapeutic nutritional supplement for oral liquid foods, tubed liquid foods, etc.

It can also be advantageously used as a skin beautifier, hair beautifier, etc.

Example 6 Powdered Yogurt After 10 kg of the crystalline α-maltose powder obtained by the method of Reference Example 4 was mixed with 2 odors of plain yogurt, it was formed into blocks and powdered in the same manner as in Example 2 to obtain powdered yogurt.

This product not only has a good flavor, but also can stabilize lactic acid bacteria for a long period of time. Therefore, this product can be advantageously used as a live bacteria intestinal regulation agent, and as a nutritional supplement for treatment such as oral liquid food and tubed liquid food.

Furthermore, it is also possible to advantageously mold the powder of this product using a granulating machine, a tablet machine, etc. to form a lactic acid bacteria preparation and use it as an intestinal regulating agent.

Example 7 Powdered medicinal ginseng extract After kneading 1.5 kg of crystalline α-maltose powder obtained by the method of Reference Example 1 with medicinal ginseng extract 5002, it was blocked and powdered in the same manner as in Example 2 to obtain a powdered medicinal ginseng extract. Obtained carrot extract.

This product was applied to a granulation machine with appropriate amounts of vitamin B1 and vitamin B2 powders to obtain vitamin-containing granular medicinal ginseng extract.

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

Example 8 Solid preparation for liquid food Crystalline α-mal obtained by the method of Reference Example 1) -750
0 parts by weight, 270 parts by weight of powdered egg yolk obtained by the method of Example 2, 209 parts by weight of skim milk powder, chloride) 4.
4 parts by weight, potassium chloride 1.85 parts by weight, magnesium sulfate 4 parts by weight, thiamine 0.01 part by weight, sodium ascorbate 0.1 part by weight, vitamin E acetate 0.
6 parts by weight and 0.0 parts by weight of nicotinic acid amide. (10) A formulation consisting of 251 parts by weight was prepared, and 251 portions of each formulation were filled into moisture-proof laminate sachets and heat-sealed to produce a liquid edible solid preparation.

This solid preparation reduces moisture in the atmosphere inside the sachet, does not require low-temperature storage, and is stable for long periods at room temperature.

Further, it has good dispersion and solubility in water.

This solid preparation is used by dissolving one bag in approximately 150 to 300 g of water to prepare a liquid food, and administering it orally or through a tube into the nasal cavity, stomach, intestines, etc.

Example 9 Solid formulation for injection Newborn hamsters were injected with antiserum prepared from rabbits by a known method to weaken the hamster's immune response, BALL-1 cells were subcutaneously transplanted, and then normal The animals were reared for 3 weeks using this method. The tumor formed under the skin was removed, cut into small pieces, and dispersed in physiological saline to loosen it. The obtained cells were cultured in serum-free R, PMI 1640 medium (+)H.
7, 2), suspended in the same medium to approximately 2x10'/-, and maintained at 35°C. After adding partially purified human interferon at a rate of 200 v'ml and keeping it for about 2 hours, Sendai virus was further added at a rate of about 300 hemagglutination titer/- and kept for 20 hours to induce human interferon. I let it happen. This is about 4°C1 about 1
．． 0005' to remove the precipitate, the resulting supernatant was further microfiltered, and the F solution was applied to an antibody column on which an anti-interferon antibody was immobilized according to a known method, and the non-adsorbed fraction was filtered. After removing the adsorbed portion, the adsorbed surface portion is eluted and concentrated through a membrane to achieve a concentration of 0. OIW/V%, specific activity 1.5 x 108 U of concentrated solution was added to about 4 liters per animal.
m7! It was obtained in a yield of .

Pyrogen-free crystalline α obtained by the method of Reference Example 1
- Pour 8 tons of maltose into a Loornt moisture-proof plastic bottle, add 0.2 fnt (approximately 3 million U) of the interferon concentrate obtained earlier, aseptically seal the cap with a rubber stopper, and inject. A solid formulation was obtained.

This production method dehydrates the interferon-containing liquid by simply dropping it onto the crystalline α-maltose powder, so it does not require freeze-drying, equipment, energy, etc., and is also effective for stabilizing interferon. It's effective and chiru.

Since this product is easily soluble in water, it can be advantageously used as a test reagent, antiviral agent, antitumor agent, etc., and as an injection for subcutaneous, intramuscular, or intravenous injections.

The activity of human interferon was measured using FL cells.
It was measured by the known plaque half-life method.

The hemagglutination titer is calculated from the book “The Jou” by J.B. 5alk.
RNA of Immunology Vol, 49
J, pages 87-98 (1944).

Example 10 Solid formulation for injection After injecting neonatal hamsters with an antiserum prepared from rabbits by a known method to weaken the immune response of the hamsters,
Cultured human-derived mononuclear cells treated with 5V-40 virus were subcutaneously transplanted, and after raising them in the usual manner for one week, 107 live BCG cells were injected intraperitoneally. The animals were kept for 2 weeks. A subcutaneous tumor of about 15 f was excised and cut into small pieces, and then suspended in trypsin-containing physiological saline to disperse and separate the cells. The cells were treated with human serum 5v/v
A cell concentration of approximately 5% was washed with Eagle's minimal basal medium, pH 7.2, and kept at 37°C.
Diluted to give XIQ6X-, and added KE and coli-derived endotoxin at a ratio of about 10 μ2/- to 1
The mixture was kept for 6 hours to induce generation of Tsumoa necrosis factor.

This was centrifuged at 4°C1 at about 1,0OOP, the precipitate was removed, and the resulting supernatant was collected at pH 7-2 and O-01M').
dialyzed against physiological saline containing phosphate buffer for 21 hours,
The Precision F solution was further concentrated and freeze-dried to obtain a powder containing Tsumoa Necrosis Factor activity.

The resulting powder was reported by G. Bodo (Symposiu
m onpreparation, 5tandari
zation and clinical use of
1nterferon, IHh Internat
ionalImmunobiological Sym
posium F3 & 9 June1977, Z
agreb, Yugoslavia) Ic, the interferon was removed by adsorption/desorption onto an ion exchanger, molecular weight fractionation by gel filtration, concentration and microfiltration, and further purified and concentrated by ammonium sulfate salting out and ConA-Sepharose affinity chromatography. Me
Highly purified tumour characterized by having hemorrhagic necrosis ability for th A sarcoma and not having any adverse effects on normal cells.
Concentration containing necrosis factor: approx. 01 w/
A concentrated solution of 30 v % was obtained from hamsters of about 30 cm.

The Tsumoa Necrosis Factor thus obtained has a specific activity of approximately 3.5×1 without contamination with the inducer used.
It was a glycoprotein with 05U.

Pyrogen-free crystalline α obtained by the method of Reference Example 4
- Collect 50P of maltose into (11) 0-capacity bottles made of meat, and add 0.5 m of the previously obtained Tsumoa Necrosis Factor concentrate (approximately 1.75 x 10
A solid preparation for injection was obtained by aseptically sealing the cap with a rubber stopper.

In this production method, a liquid containing TSUMOA Necrosis Factor is dehydrated into crystalline α-maltose powder, so that it not only does not require treatments such as freeze-drying, but is also effective in stabilizing TSUMOA Necrosis Factor.

Since this product is easily soluble in water, it can be advantageously used as an antitumor agent, nutritional supplement, etc., and as an injection for intravenous drips.

In addition, the activity of Tsumoa Necrosis Factor is E,
PicksTumor Necrosis Facto
r in” Lymphokines” Vol.I
I, pp235-272. Aca-demic p
ress (1981). Tsumoa
A known method was used to measure the number of surviving cells after culturing for a certain period of time using necrosis factor-sensitive L-929 cells.

Example 11 Crystalline α-maltose 500 obtained by the method of Reference Example 3
50 m of methanol in which iodine 32 was dissolved was added to f and mixed, further 200 m of a 10 w/w% pullulan aqueous solution was added and mixed, and the mixture was left overnight at room temperature to convert into β-maltose hydrated crystals, resulting in a moderate amount of A plaster for wound treatment that spreads and exhibits adhesive properties was obtained.

This product can be used to treat injuries such as cuts, wounds, burns, etc. by measuring it directly on the wound surface or applying it to gauze, oiled paper, etc.

In addition, this product not only has a bactericidal effect using iodine, but also acts as a nutritional supplement for cells using maltose, which shortens the healing period and allows the wound surface to heal cleanly.

(Effect of the invention) As is clear from the above, the crystalline α-
Maltose is used in pharmaceuticals such as nutritional supplements and physiologically active substances,
The method of manufacturing pharmaceuticals by converting it into β-maltose hydrated crystals and dehydrating it in raw materials or processing intermediates does not require harsh conditions such as heating and drying, so the active ingredient is decomposed and the activity is reduced. It is possible to easily produce stable, high-quality pharmaceuticals without causing deterioration such as deterioration.

The obtained dehydrated pharmaceutical products are prevented from being contaminated by microorganisms and are prevented from undergoing deterioration such as hydrolysis, rancidity, and browning, so that the life of the product can be stably maintained over a long period of time.

[Brief explanation of drawings]

FIG. 1 shows an X-ray diffraction pattern of an amorphous powder with an α-maltose content of 48.0 W/W%. FIG. 2 shows an X-ray diffraction pattern of a crystalline powder with an α-maltose content of 55.6 W/W%. Figure 3 shows the α-maltose content (10). An X-ray diffraction pattern of a crystalline powder with a concentration of 4 w/w% is shown. FIG. 4 shows an X-ray diffraction pattern of a crystalline powder with an α-maltose content of 68.7 w/w%. FIG. 5 shows an X-ray diffraction pattern of a crystalline powder with an α-maltose content of 74.2 W/W%. Figure 6 shows β-maltose hydrated crystals (maltose HHH
) shows the X-ray diffraction pattern of the powder.

Claims (12)

[Claims] (1) A dehydrated drug in which a drug, its raw material, or a processing intermediate contains crystalline α-maltose and is converted into a hydrated β-maltose crystal. (2) The dehydrated pharmaceutical according to claim (1), wherein the crystalline α-maltose contains 55 w/w % or more of the optical isomer α-maltose. (3) Crystalline α-maltose is 85w/w per solid substance
The dehydrated pharmaceutical according to claim 1 or 2, which is crystallized from high purity maltose containing % or more of maltose. (4) The dehydrated pharmaceutical according to claim (1), (2) or (3), wherein the crystalline α-maltose is a powder. (5) The crystalline α-maltose has a moisture content of less than 3 w/w%.
Dehydrated pharmaceuticals described in paragraph 2), paragraph (3) or paragraph (4). (6) Claims (1), (2), and (3) characterized in that the dehydrated pharmaceutical contains gelatinized starch, alcohol, an oil-soluble substance, or a physiologically active substance. section,
Dehydrated pharmaceuticals described in paragraph (4) or (5). (7) A method for producing a dehydrated pharmaceutical product, which comprises adding crystalline α-maltose to the pharmaceutical product, its raw materials, or processing intermediates and converting it into β-maltose hydrous crystals. (8) The method for producing a dehydrated pharmaceutical according to claim (7), wherein the crystalline α-maltose contains 55 w/w% or more of the optical isomer α-maltose. (9) Crystalline α-maltose is 85w/w per solid substance
% or more of maltose, the method for producing a dehydrated pharmaceutical according to claim 7 or 8, wherein the dehydrated pharmaceutical is crystallized from high-purity maltose containing % or more of maltose. (10) The method for producing a dehydrated pharmaceutical according to claim (7), (8) or (9), wherein the crystalline α-maltose is a powder. (11) Crystalline α-maltose has a moisture content of less than 3 w/w, Claims (7) and (
The method for producing a dehydrated pharmaceutical according to item 8), item (9), or item (10). (12) Claims (7), (8), and (9) characterized in that the dehydrated pharmaceutical contains gelatinized starch, alcohol, an oil-soluble substance, or a physiologically active substance. The method for producing a dehydrated pharmaceutical according to item (10) or item (11).