JPS62138425A - Dehydrated medicine and production thereof - Google Patents

Abstract

PURPOSE:To readily obtain a high-quality and stable dehydrated medicine, by incorporating anhydrous maltose in a medicine, raw material therefor or processed intermediate material thereof, converting the water in the hydrous material into beta-maltose hydrous crystals and dehydrating the hydrous material. CONSTITUTION:For example, anhydrous maltose, particularly containing >=85w/w%, based on the solid material, maltose is incorporated in a medicine, e.g. nutriment, physiologically active material agent, germicide, etc., raw material therefor or processed intermediate material thereof to dehydrate the hydrous material. The anhydrous maltose is capable of converting water in various kinds of hydrous materials into beta-maltose hydrous crystals to substantially reduce the water therein and dehydrate the hydrous material. Crystalline anhydrous alpha-maltose, crysalline beta-maltose, amorphous anhydrous maltose, etc., may be preferred as the anhydrous maltose. The anhydrous maltose acts also as a stabilizer and is capable of producing a high-quality and stable dehydrated physiologically active material agent.

Description

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

More specifically, pharmaceuticals, their raw materials or processing intermediates,
Production of a dehydrated pharmaceutical product containing anhydrous maltose to convert β-maltose into hydrated ice crystals, and a dehydrated pharmaceutical product characterized by containing anhydrous maltose in a pharmaceutical product, its raw material or processing intermediate to convert β-maltose into hydrated ice crystals. Regarding the method.

(General technology) Conventionally, [1! Various pharmaceuticals such as nutritional supplements, physiologically active substances, and bactericides are used to increase f, treat injuries and diseases, and promote recovery.

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

Generally speaking, drying methods inevitably result in quality deterioration during the process, and the current situation is that only nutrients with poor flavor can be obtained.

In addition, for example, physiologically active substances such as lymphokines, hormones, vitamins, probiotics, enzymes, and antibiotics are unstable in the coexistence of high water, so they are usually required to be used in large quantities in order to improve their stability. It is commercialized by drying methods such as heat drying and vacuum drying in the presence 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 these water-soluble polymer compounds is extremely difficult and not only wastes a great deal of energy, but also causes the resulting dried product to become water-soluble and contain physiologically active substances. There is a risk of causing a decrease in activity.

(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 have carefully considered its use.

As a result, anhydrous maltose, especially 85 per solid
By incorporating anhydrous maltose containing maltose of w/x or more into hydrated substances such as hydrated nutrients and hydrated physiologically active substances and converting it into β-maltose hydrated ice crystals, anhydrous maltose acts as a powerful dehydrating agent. The present invention was completed by confirming that stable pharmaceutical products can be easily produced without deterioration of quality.

The present invention focuses on anhydrous maltose, which has not received any attention as a dehydrating agent in the past, and a method of containing this anhydrous maltose as a dehydrating agent and dehydrating a water-containing substance is the subject matter of the present invention.

The method for dehydrating hydrated materials according to the present invention is preferable as a method for dehydrating things that contain water, especially those that contain free water that is different from bound water such as crystallized water, such as dry nutrients. 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 anhydrous maltose is contained in these hydrated substances, the anhydrous maltose strongly takes in about 5x of the water in the mold dish as crystal water of the β-maltose hydrated crystals, and
It has been found that the water content of hydrated materials is substantially reduced and dehydrated.

For example, by placing anhydrous maltose filled in a moisture-permeable pouch made of paper or the like in a moisture-proof container containing a dry nutritional supplement such as a solid preparation for liquid food, the relative humidity inside the container can be extremely reduced. It was found that the product was of high quality and could be stably maintained for a long period of time.

At this time, anhydrous maltose captures water and is converted into β-maltose hydrated crystals, and even after the conversion, it does not become sticky or runny, making it difficult to store dry nutrients or waterproof containers. There is no need to worry about contamination.

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

In addition, for example, in the case of high-moisture nutrients such as liquids such as fresh cream and egg yolks, or pastes, the water content is substantially reduced by incorporating anhydrous maltose and converting it into hydrated β-maltose crystals. High-quality dehydrated nutritional supplements such as maskitic and powdered nutritional supplements can be produced very easily. Since this method does not require harsh conditions such as heating and drying, it can easily convert liquid or pasty high-moisture nutrients into dehydrated nutrients with good flavor and reduced moisture content without degrading or degrading them. It has characteristics.

In addition, at this time, anhydrous maltose is added in an amount commensurate with the water content contained in these raw materials, and anhydrous maltose is partially converted to β-maltose hydrated crystals.In other words, anhydrous maltose is added together with β-maltose hydrated crystals. When a dehydrated nutritional supplement containing . It has been found that the interior of the container can be maintained in a highly dry state.

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.

In addition, in the case of paste-like physiologically active substances such as aqueous solutions of lymphokines and antibiotics, medicinal ginseng extracts, and stupa extracts, anhydrous maltose is added to the β-
By converting the maltose into hydrated crystals, high-quality dehydrated physiologically active substance agents with substantially reduced water content, for example, physiologically active substance agents in the form of mascuit or powder, can be produced very easily.

This method does not require harsh conditions such as heating and drying,
Moreover, since anhydrous 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 waste 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 anhydrous maltose can be found in a vial, and an aqueous solution containing a physiologically active substance such as a lymphokine or a hormone can be added to the vial in order to convert the anhydrous maltose into hydrated β-maltose crystals. It is also advantageous to add a smaller amount of water than the amount of water used and seal the container tightly to produce a solid preparation for injection.

In this case, it has been found that anhydrous maltose can not only dehydrate the water '+8 M containing the physiologically active substance, but also dehumidify and dry the atmosphere inside the vial.

As a result, the dehydrated pharmaceutical product 1q of the present invention not only has an easy manufacturing process, but also can stably maintain its high quality over a long period of time, and furthermore, dissolves quickly in water upon use. It was also found that it has the following characteristics.

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

Prior to the present invention, the present inventors studied anhydrous maltose, particularly a method for producing anhydrous maltose powder.

First, we conducted a detailed study on anhydrous maltose for use as a dehydrating agent, and found that it was 85 w/w/solid.
It has been found that high purity maltose of w% or higher is suitable.

High purity maltose as a raw material may be prepared by using commercially available β-maltose hydrous 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
A method of collecting high-purity maltose by allowing β-amylase to act on gelatinized or liquefied starch and separating the generated maltose from polymer dextrin, as disclosed in Japanese Patent Publication No. 7078, etc., or, for example, Japanese Patent Publication No. 13089-1989 There is a method of collecting high-purity maltose by allowing starch debranching enzymes such as isoamylase 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. 513-28154, etc. maltose is produced by the action of the enzyme that is
For example, it is convenient to further increase maltose purity by a method such as removing contaminant sugars by column fractionation using a salt-type strongly acidic cation exchange resin as disclosed in JP-A-58-23799. Further, this fractionation method may be a fixed bed method, a moving bed method, or a pseudo moving bed method.

Next, 85 v/w% per solid matter obtained in this way
A method for producing anhydrous maltose from the above-mentioned high-purity maltose will be described.

Suitable examples of anhydrous maltose include crystalline anhydrous α-maltose, crystalline β-maltose, and amorphous anhydrous maltose.

In order to produce crystalline anhydrous α-maltose powder, for example, as described in previously filed Japanese Patent Application No. 156,744/1980, these high purity maltose are reduced to about 1% water content.
less than 0 w/wχ, preferably 2. Ow/w% or more9
．． It may be produced by preparing a high-concentration silica with a concentration of less than 5 w/wχ, and crystallizing α-maltose from this silica while maintaining the temperature in the range of 50° C. to 130° C. in the coexistence of seed crystals to form a powder.

In addition, to produce crystalline anhydrous β-maltose powder,
For example, a method may be employed in which the β-maltose water-containing ice crystal powder is vacuum-dried under conditions that do not melt the powder, for example, at a temperature of about 80 to 110°C.

In addition, in order to produce amorphous anhydrous maltose powder, for example, commercially available β-maltose hydrated crystals may be used as a raw material, or it may be produced using a high purity maltose aqueous solution with a concentration of 85 v/v or more per solid substance. Bye.

When commercially available hydrated β-maltose crystals are used, they may be produced by drying under atmospheric pressure or under reduced pressure at a temperature where they melt, for example at a temperature of about 120 to 150°C, and then pulverizing them. In addition, when using a high-purity maltose aqueous solution, for example, it is produced by vacuum drying or freeze-drying Shirabu with a concentration of about 70 to 95 w/vχ and then pulverizing; It is also advantageous to directly produce a powder using a spray drying method such as a high-pressure nozzle method or a rotating disk method.

The anhydrous maltose powder of the present invention produced in this way is a white powder with an elegant low sweetness, has a low water content, is substantially anhydrous, and is usually produced by the Karl Fischer method.
It is less than 3 w/wχ, preferably less than 2 w/wχ, and although its fluidity varies somewhat depending on the shape and size of the powder particles, it is substantially fluid.

Furthermore, the anhydrous maltose referred to in the present invention may be any substantially anhydrous maltose that is converted into β-maltose hydrated crystals and exhibits a strong dehydration effect; for example, anhydrous maltose that promotes the conversion of anhydrous maltose to β-maltose hydrated crystals. In order to enhance the effect as a dehydrating agent, a substantially amorphous anhydrous maltose powder coexisting with β-maltose hydrate crystals as small as possible as seed crystals, usually less than 5 w/w x, preferably less than 1 w/w x. It can also be advantageously implemented.

When the anhydrous maltose powder obtained in this way is incorporated into a water-containing substance such as food, medicine, cosmetics, or industrial chemicals, the water contained therein is captured as water of crystallization in the β-maltose hydrous crystals. , was found to act as a strong dehydrating agent for fixing and hydrated materials.

Anhydrous maltose differs from conventionally commercially available β-maltose hydrated crystals (Hayashibara Co., Ltd., registered trademark [Sunmalt]) in that it can be used not only with water but also with organic acid aqueous solution, saline water ID solution, protein water 16 solution, emulsified It has been found that it can be rapidly dissolved in various aqueous solutions such as liquid and alcohol solution at high concentrations.

This property makes it convenient to use anhydrous maltose as a dehydrating agent to produce various dehydrated products with reduced moisture content from various hydrated materials.

The dehydrating agent of the present invention can be advantageously applied when dehumidifying and drying the atmosphere inside a moisture-proof container, and in addition, when dehumidifying and drying the atmosphere inside a moisture-proof container, and furthermore, when dehydrating or drying the atmosphere in a moisture-proof container, and when containing water-containing substances that are easily accompanied by deterioration or deterioration during processes such as heat drying or vacuum drying, or that are difficult to dry. There are cases where high-quality dehydrated products such as maskite-like or powder-like products are manufactured from materials.

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, agricultural products such as raw chestnuts, juices, vegetable extracts, soy milk, nut paste, and gelatinized starch paste; marine products such as sea urchin paste, oyster extract, and sardine paste; Raw eggs, lecithin, milk, whey, fresh cream, yogurt, butter, livestock products such as cheese, sweeteners such as maple syrup, honey, alcoholic beverages such as sake, wine, medicinal liquor, etc. Stable, high-quality dehydrated nutrients can be easily produced from substances.

In addition, in the case of physiologically active substance agents, their raw materials or processed intermediates, interferon, lymphotoxin, Tumore necrosis factor, macrophage migration inhibitory factor,
Solution containing lymphokines such as colony stimulating factor, transfer factor, interleukin II, insulin, growth hormone, prolactin, erythropoietin,
Solutions containing hormones such as follicle stimulating hormone, BCG vaccine, Japanese encephalitis vaccine, tetanus toxoid, hub antitoxin, biological products such as human immunoglobulin, antibiotics such as penicillin, erythromycin, chloramphenicol, tetracycline, streptomycin, kanamycin sulfate. Liquids containing substances, liquids containing vitamins such as thiamine, riboflavin, ascorbic acid, cod liver oil, carotenoids, ergosterol, tocopherol, etc., liquids containing enzymes such as lipase, elastase, urokinase, protease, β-amylase, isoamylase, glucanadi, lactase, etc. Extracts such as medicinal ginseng extract, stupa extract, chlorella extract, aloe extract, and licorice extract, as well as liquids and pastes such as lactic acid bacteria and yeast paste, are stable and highly effective without losing their active ingredients or activity. High quality dehydrated physiologically active substance preparations can be easily produced.

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

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, and even as an enzyme detergent.

As a method for incorporating anhydrous maltose into a hydrous material, known methods such as mixing, kneading, dissolving, permeating, scattering, coating, spraying, and injecting can be used as appropriate until the desired dehydrated product is completed. To be elected.

The amount of anhydrous maltose to be added to the hydrated material can be changed depending on the moisture contained in the hydrated material and the properties of the desired dehydrated product, but it is usually 0.5% per part by weight of the hydrated material.
01 to 500 parts by weight, preferably 0.1 to 100 parts by weight. At this time, in order to further improve the quality of the obtained dehydrated pharmaceutical, it is also advantageous to use appropriate flavoring agents, coloring agents, flavoring agents, stabilizers, fillers, etc. in combination. - In particular, regarding stabilizers, since the present invention is a strong dehydration method using anhydrous maltose, there is no need to limit the stabilizers to low molecular compounds such as antioxidants, which are difficult to dry in the past! "Existing water-soluble polymer compounds, such as soluble starch, dextrin, cyclodextrin, pullulan, ercinan, dextran, (guntan gum, gum arabic, locust pea gum, guar gum, tragacanth gum, tamarind gum, carboxymethyl cellulose, hydroxyethyl cellulose, Substances such as hydroxyethyl starch, pectin, agar, gelatin, albumin, and casein 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 paste-like hydrated material in advance, and then uniformly containing anhydrous maltose therein by a method such as mixing or kneading,
A dehydrated article is obtained in which fine β-maltose hydrous crystals are precipitated.

Ice crystals contain aroma components, active ingredients, etc. derived from water-containing substances that are coated with a film of a polymer compound, or are encapsulated together with fine β-maltose water-containing crystals in microcapsules surrounded by the film. In addition, when using cyclodextrin, clathrate compounds etc. are formed and their volatilization,
Since quality deterioration is prevented, it is extremely superior 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, for relatively high moisture content such as pharmaceuticals, their raw materials, or processing intermediates,
After uniformly containing anhydrous maltose to a water content of 30 v/v % or less, preferably about 5 to 25 w/wχ, it is left in a vat or the like for about 1 to 10 days at about 10-50°C, e.g., at room temperature. Then, it may be converted into β-maltose hydrous crystals, solidified, for example, in the form of a block, 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 crushing.

Further, a powder product can also be directly produced by a spraying method or the like. For example, while fluidizing anhydrous 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 aged at about 30 to 60°C for about 1 to 24 hours to form β- Powder obtained by converting anhydrous maltose into hydrated maltose crystals, or by spraying it immediately after mixing anhydrous maltose with a liquid or paste-like hydrate, or after starting the conversion into hydrated β-maltose crystals. A method of producing a powder product by similarly ripening the product and converting it into β-maltose hydrous crystals is suitable as a method for producing large mice.

In the case of this spraying method, in order to promote the conversion of anhydrous maltose into β-maltose hydrated crystals, as small a quantity of β-maltose hydrated crystals as possible are allowed to coexist as seed crystals together with anhydrous maltose, thereby shortening the ripening period. It can also be carried out advantageously.

The powdered dehydrated pharmaceutical product obtained in this way has the following characteristics:
i- or, if necessary, in combination with fillers, excipients, binders, stabilizers, etc., and further into appropriate shapes such as granules, tablets, capsules, rods, plates, cubes, etc. You can also freely mold and use it.

In addition, 1" of water containing pharmaceutical intermediates such as granules and uncoated tablets as a core, and an appropriate amount of an aqueous solution of anhydrous maltose, preferably a binder such as a water-soluble polymer, coexisting with the core is about 70 to 95 w/w%. It is also advantageous to manufacture a sugar coating by coating the δ liquid and then converting it into β-maltose hydrous crystals and crystallizing them.

In addition, when anhydrous maltose is added to a high moisture content by mixing, kneading, etc., when the anhydrous maltose is converted to β-maltose hydrated crystals and dehydrated, the volume decreases as the anhydrous maltose is converted to β-maltose hydrated crystals. Expand. When the expansion is significant, it reaches about 1.5 to 4.0 times. In this way, products that expand and solidify have lower hardness and are easier to powder than products that expand less, have less wear on cutting machines and crushers, and consume significantly less power. It has the advantage of saving money.

Moreover, by utilizing this expansion phenomenon, dehydrated foods of various shapes can be manufactured. For example, a high moisture content containing anhydrous maltose is placed in plastic containers of various shapes such as flowers, birds, fish, dolls, etc., and left at room temperature for about 5 to 90 hours to expand and solidify. By this method, dehydrated articles of various shapes can be obtained. If necessary, to further promote this expansion, an easily vaporized solvent such as alcohol, a blowing agent that generates carbon dioxide gas, etc. may be included together with the anhydrous maltose, and the mixture may be heated slightly.

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

In addition, in general, kako requires a large amount of water in order to swell and gelatinize. Therefore, gelatinized starch is extremely susceptible to microbial staining. Anhydrous maltose can also be advantageously used as a dehydrating agent for such gelatinized starch. By containing anhydrous maltose and converting it into hydrated β-maltose crystals, water content is substantially reduced and microbial contamination can be prevented.

In addition, anhydrous maltose is easily and uniformly mixed with gelatinized starch and acts as an anti-aging agent, so it can significantly extend the product life of various processed nutrients containing gelatinized starch. can.

Anhydrous maltose also shows high affinity for AJ15 col. Due to this property, methanol, ethanol,
It can also be advantageously used as a dehydrating agent for water contained in alcohol or alcohol-soluble substances such as butanol, propylene glycol, glycerin, and polyethylene glycol. For example, mascit-like products are produced by dehydrating alcohol-containing hydrates such as medicinal liquor with anhydrous maltose, and retaining the active ingredients, aroma, etc. in the β-maltose hydrate crystals produced.
Dehydrated pharmaceuticals, such as powders, can be advantageously produced.

In addition, active ingredients such as iodine can be stabilized by mixing alcohol-soluble ((l) such as iodine with anhydrous maltose and adding an aqueous solution containing water-soluble polymers etc. to this to convert it into β-maltose hydrous crystals. It is also possible to advantageously produce a mask-like ointment having appropriate viscosity, spreadability, and adhesion.

Furthermore, although anhydrous maltose is a hydrophilic carbohydrate, it exhibits surprisingly large lipophilic properties.

Due to this property, anhydrous 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, mustard oil, sesame oil, safflower oil, palm oil, cocoa butter, beef tallow, lard, starch fat, fish oil, hydrogenated oil, citrus essential oil, flower essential oil, spices oil, peppermint oil, spearmint oil, natural spices such as kola nut extract, coffee extract, β-carotene, paprika color,
Oil-based young colors such as annatto pigments and chlorophyll:
I, cod liver oil, vitamin A1 Vitamin B21ffi acid ester, vitamin E, vitamin 1 oil such as vitamin D 1 oil-soluble oil such as ancient vitamins, estrogen, progesterone, androgen, prostaglandin; L lumon, linoleic acid, linol It can be advantageously used as a dehydrating agent that powerfully captures trace amounts of water contained in acids, highly unsaturated fatty acids such as arachidonic acid, eicosabenenoic acid, and docosahexaenoic acid.

Oil-soluble substances dehydrated with anhydrous maltose are of high quality and have the characteristic of being less susceptible to quality deterioration such as hydrolysis and deterioration.

It is also advantageous to impregnate anhydrous maltose with an oil-soluble substance or add it to Al to produce powdered nutritional supplements, powdered vitamins, hormones, and other physiologically active substances.

In this case, anhydrous maltose acts not only as a dehydrating agent but also as a stabilizer, holding agent, excipient, carrier, etc.

Amorphous anhydrous maltose is also advantageously used in foods containing useful 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 discovering that anhydrous maltose strongly dehydrates various water-containing substances, and by using the anhydrous maltose as a dehydrating agent, it can be High-quality nutritional supplements with reduced water content without degrading or volatilizing the flavor and aroma from water-containing substances such as hydric substances, and high-quality nutritional supplements with reduced water content without degrading or reducing the active ingredients and activity. Pharmaceutical products such as physiologically active substance agents can be advantageously produced.

In addition, anhydrous maltose is used not only in the special cases mentioned above, but also as maltose, which is a natural sweetener that induces tooth decay.
There are no concerns about increases in blood cholesterol, and it also has properties such as elegant sweetness, body, shine, viscosity, and water retention, making it advantageous for manufacturing nutritional supplements for oral use. Available.

Furthermore, anhydrous maltose is maltose, which is a nutrient that is originally metabolized and utilized.

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.

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

Experiment 1. The raw material maltose for comparison of I4 maltose is '?' manufactured by Hayashibara Co., Ltd. shown in Table 1. ! R-type starch seeds and powdered sugar products.

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

Product name Sunmalt ■, Maltose 1], Maltose 1
111. In the case of powder products such as β-maltose hydrated crystals such as maltose It HI+, they are heated and dissolved in a small amount of water, then placed in an evaporator and boiled under reduced pressure to reduce the moisture content to 4.
．． 5 w/vχ.

The high-concentration silica with a water content of approximately 4.5 w/w% obtained in this manner is transferred to a crystal assistant, and high-purity β-
About 50% of maltose hydrated crystals (maltose H) Il+)
w/vχ Crystalline anhydrous α-maltose crystallized and collected from a hot methanol solution was added as a seed crystal for 2 w/wχ, and 1
The mixture was subjected to IJT at 20° C. for 20 minutes, stirred, and then taken out into an aluminum vat and aged at 90° C. for 16 hours to prepare a block. Next, it was cooled and ground in a chamber 1 quarry to obtain a powder product. Further, β-maltose hydrate crystals (product name B: Maltose 111111) were vacuum-dried by the method of Reference Example 5 to obtain a powder product of crystalline anhydrous β-maltose. Further, β-maltose hydrate crystals (trade name: Maltose HHH) were heated and dissolved in a small amount of water, and dried in vacuum according to the method of Reference Example 5 to obtain a powder product of amorphous anhydrous maltose. Using these powder products, C. C. Sweeley et al., Journal
al o “American Chemical 5o
vol. 85, pp. 2497-2507 (1'
) Gas chromatography was performed according to the method described in 1963) to determine the content of the optical isomer α-maltose in maltose, and F, 11.5 todol
a et al,, Journal of Ameri
An X-ray diffraction apparatus (manufactured by Rigaku Denki Co., Ltd., trade name Geigerflex RΔD-118, CuKa
The presence or absence of crystals was examined by powder X-ray diffraction. The results are shown in Table 1. The X-ray diffraction pattern is
It is shown in Figure 6. Figure 1 shows α-maltose-containing l148w/
Figure 2 shows the α-maltose content of the amorphous powder, which is 55.6 v/Vχ.
Figure 4 shows the α-maltose content B 8 ,7 w/w of a crystalline powder with a maltose content of 61.4 w/wχ.
Figure 5 shows the crystalline powder wχ containing α-maltose.
FIG. 6 is an X-ray diffraction pattern of crystalline anhydrous β-maltose powder.

Further, amorphous anhydrous maltose showed the same X-ray diffraction pattern as shown in FIG. In addition, as a control experiment, the X-ray diffraction pattern of FIG. 7 was obtained by X-ray diffraction of the raw material β-maltose frozen product (maltose 111111) powder.

As is clear from the results in Table 1, those in which new crystal precipitation was observed by X-ray diffraction showed a content of the optical isomer α-maltose of 55 w/w% or more, and the raw material maltose was , maltose content is 85% solids
It has been found that more than w/w% is necessary.

Experiment 2. Comparison of dehydration power of various sugars Anhydrous glucose, sugar, various anhydrous sugars prepared in Tests NQ1 to 8 of Experiment 1, or β-maltose hydrated ice crystals used as the raw material for Test Nα5, with a particle size of approximately 100 to 150
1 g of each powder was taken into a plastic Petri dish with a diameter of 5 cm, and the relative humidity was adjusted to 70χ.
The water content of these sugars (X
) was measured to compare the strength of dehydration power.

The results are shown in Table 2.

As is clear from the results in Table 2, 85v/solid
Anhydrous maltose containing maltose of v % or more is
It has been found to act as a strong dehydrating agent up to the point where it has acquired water up to about 5 v/wx of its weight.

Furthermore, when the X-ray diffraction patterns of each sample were examined and compared over time, there was no change in anhydrous glucose, sugar, and hydrated β-maltose crystals. However, it has been found that anhydrous maltose with Na 3 to 8 traps moisture, converts about 5% of moisture into β-maltose hydrated crystals, reaches an equilibrium moisture content, and becomes stable.

In addition, in the same manner, anhydrous maltose prepared with NO3 in Experiment 1 was placed in an atmosphere at 25°C with a relative humidity of 921 MW, and its moisture content (χ) was measured over time.
It was found that even after converting into β-maltose hydrated crystals at a moisture content of 18% moisture, the crystals contained moisture and stabilized by reaching equilibrium at a moisture content of about 18χ. In this case, it remains powdery and does not get wet or
No flowing phenomenon was observed.

Because of this property, it has been found that anhydrous maltose can be advantageously used as a dehydrating agent for pharmaceuticals such as nutritional supplements and physiologically active substances, raw materials thereof, and processing intermediates.

Experiment 3. Various uses of each monosaccharide in sunto cream υ
! Sand cream was prepared using the following products and their dehydrating effects were compared.

As various sugars, anhydrous glucose, sugar, crystalline anhydrous α-maltose prepared in Test NQ5 of Experiment 1, or β-maltose hydrated crystals as its raw material were used.

The preparation method is to take 425g of shortening in a mixer, add 500g of sugar to it, mix it, then add a melted mixture of 25g of soybean oil (white squeezed oil) and 50g of cocoa butter, and pour it into a sandwich. It was creamy.

Note that when β-maltose hydrous crystals were used as the saccharide, it could not be mixed and a sand cream could not be produced.

The obtained sandwich cream to relative 2 degrees 92χ? Aizi
The sand cream was left in a harsh atmosphere at 29° C., and its moisture content (χ) was measured over time to observe the condition of the sandwich cream.

The results are shown in Table 3.

Table 3 *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 3, the humidity is adjusted to 92χ! i! Even under the harsh conditions of 29℃, the sand cream made with anhydrous maltose did not lose its shape, and the anhydrous maltose used was β-mal!・It was found that the moxibustion is converted into hydrated crystals, and stabilized by reaching equilibrium with the atmospheric conditions. From this fact, the prepared sand cream can be reduced by simply trapping the moisture in the atmosphere, dehydrating it and reducing the relative humidity of the atmosphere by, for example, baking it in kutsky, biscuits, etc. and storing it in a moisture-proof container. without causing any deterioration in the quality of the sandwich cream itself.
It was also found that it could be maintained stably for a long period of time.

This property can be advantageously utilized in the production of pharmaceuticals containing oil-soluble substances.

Experiment 4. Comparison of $11r3 quality against gelatinized starch Dissolve 400 g of mochi in 6 ooml of water, pour it into a wooden frame lined with Ichisan, and steam it at 105°C for 10 minutes to obtain gelatinized starch.

In addition, crystalline anhydrous α prepared with test Na5 in Experiment 1
-Mix 800 g of maltose, or its original i-+ β-, maltose hydrated crystals with a mixer, and when it becomes homogeneous, add 200K of starch syrup and mix well! Knead, shape, and then dry lightly with warm air at 40℃ for 2 hours to form the gyuhi.
! J.

When ice crystals were left open to room temperature of 25°C, black mold colonies were observed after 12 days with the ice crystals using β-maltose-containing hydrous bonds, but when crystalline anhydrous α-maltose was used, black mold colonies were observed. Even after 20 days, no microbial contamination was observed.

In addition, when we cut the product after 20 days and observed its cross section, we found that the product using crystalline anhydrous α-maltose was
Although the surface layer was slightly hardened and crystals were precipitated, the inside was translucent, as it was immediately after production, and had appropriate gloss and viscosity. The crystals in the surface layer were found to be crystalline anhydrous α-maltose or β-maltose which had been converted into hydrated ice crystals from the X-ray diffraction pattern.

On the other hand, when using β-maltose hydrated ice crystals, mold had just formed on the surface, and the entire cross section was cloudy and lacked luster.

As a result, it was found that anhydrous maltose acts as a dehydrating agent for gelatinized V dressings, prevents microbial contamination, and further prevents aging of gelatinized V dressings.

This property can be advantageously utilized in the production of pharmaceutical products containing gelatinized starch.

Hereinafter, a method for producing anhydrous 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 to 130°C to stop the enzyme reaction and reduce the OE to about 0.
A liquefied liquid of No. 5 was obtained. This starch liquefied liquid was rapidly cooled to 55°C to produce Pseudomonas amyloderamosa (Pseudomonas amyloderamosa).
nas amyloderamosa) ATCC21
From the culture solution of 202, H made t, t:i/'? mirror t'
(EC3,2,1,88) &El 100 units per tile and β-amylase derived from soybean (EC3,2,1,2)
(Nagase Sangyo ■, product name n 1500) is the same.
50 units and saccharified for 40 hours while keeping the pH at 5.0.
A high-purity maltose liquid with a maltose content of 92.5 w/wx per solid was obtained, which was decolorized with activated carbon and desalted and purified with an ion exchange resin. This maltose solution has a concentration of 75χ
After soaking in a cotton, put it in a auxiliary crystal can, add 1χ of powdered seed crystals of β-maltose heptubiderite crystals, bring it to 40°C, slowly cool it while stirring, lower it to 30°C for 2 days, and put it in a basket. The honey was separated using a type centrifuge, and the crystals were sprayed and washed with a small amount of water to obtain highly pure β-maltose hydrous crystals with a purity of 99.0%.

The high-purity maltose obtained in this way was heated and dissolved in a small amount of water, then placed in an evaporator, boiled under positive pressure,
Shirub with a moisture content of 5.5 w/v% was prepared. Next, the crystalline anhydrous α-maltose obtained by the method of Experiment 1 and Test NQ6 was added to the rack machine at a rate of 1 w/w per solid solid material.
Add wχ and CI'l at 100℃ for 5 minutes! Auxiliary crystallization, then taken out into a plastic vat and aged at 70°C for 6 hours to form a block. Made by A.

Next, this block was crushed with a cutting machine, washed and dried, and the optical isomer α-maltose content was 73.3w/wχ
Crystalline anhydrous α-maltose powder with a moisture content of 0.42 w/wχ was obtained in a yield of about 92 w/wχ based on the high purity β-maltose hydrous crystals of Original 51.

Ice crystals can be advantageously used as a dehydrating agent for hydrated products such as the pharmaceutical of the present invention, its raw materials, or processing intermediates.

Reference Example 2 A high-purity maltose aqueous solution with a maltose content of 92.5 w/vχ per solid substance prepared by the method of Reference Example 1 was concentrated under reduced pressure to a moisture content of 20 w/wχ, and then transferred to a high-pressure pump from the top of a spray drying tower. The mixture is sprayed from a nozzle, dried with hot air at 100°C, and placed on a moving wire mesh conveyor at the bottom of the drying tower.
It was dropped onto a fluidized crystalline anhydrous α-maltose powder in advance, and while blowing hot air at 70°C from the bottom of the conveyor, it was gradually moved outside the drying tower and taken out after 60 minutes. Powder? The product was packed in a 11-component column and exposed for 4 hours while blowing hot air at 70°C, and the 7-in-1 product was produced.
A crystalline anhydrous maltose content of /wχ was obtained in a yield of about 94χ based on the high purity maltose of Original 4.

Ice crystals, like the anhydrous maltose powder obtained by the method of Reference Example 1, can be advantageously used as a dehydrating agent for various hydrated substances.

Reference Example 3 Commercially available fine FA liquefied α-amylase was added to a suspension of 2 parts by weight of cornstarch and 10 parts by weight of water, and after gelatinization by heating to 90°C, the enzymatic reaction was carried out by heating to 130°C. Stop, DE
The starch liquefied liquid was heated to 55°C to make a 1fk liquid of about 2.
domonas ayloderamosa) A
120 units of isoamylase (EC3,2,1,68) prepared from the culture solution of TCC21262 per starch tile,
Add the same <30 units of β-amylase from soybean,
Saccharification was carried out for 36 hours while maintaining the Pl+5.0, and purification was performed in the same manner as in Reference Example 1 to obtain a high purity malt-smid solution with a maltose content of 88.6 w/wχ.Then, it was concentrated under reduced pressure to reduce water content to 3. It was set as 5 w/v% Shirabu.

Next, the crystalline anhydrous α-maltose obtained by the method of Reference Example 2 was transferred to a auxiliary crystallizer, and 2.5% of the crystalline anhydrous α-maltose obtained by the method of Reference Example 2 was added thereto.
w/wχ was added, stirred at 120°C for 10 minutes, then taken out into an aluminum vat, 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 the optical isomer α. - Crystalline anhydrous α-maltose powder with a maltose content of 63°9 w/v% and a water content of 0.60 w/wχ is prepared as raw material! It was obtained in a yield of about 94x based on 71 high purity Mars.

Similar to the anhydrous maltose powder obtained by the method of Reference Example 1, quartz crystal can be used as a dehydrating agent for various hydrated substances.

Reference example 4 Maltose content 79. [3% starch sugar solution (manufactured by Hayashibara Co., Ltd., trade name t1) l-75] at δ degree 45 v/v
% aqueous solution and made it the raw sugar. For fractionation (5 (fat is alkali metal type strong acid cation exchange 11 fat (manufactured by Tokyo Organic Chemical Industry Co., Ltd., trade name XT-1022E, Na + type), a jacketed stainless steel column with an internal diameter of 5.4 cm was used. was filled in the form of an aqueous suspension.At this time, the resin layer length was 5I1.
The resin layer was packed into four columns of No. 1, and the four columns were connected so that the liquid flowed in series, making the total length of the resin layer 20 m.

While maintaining the internal temperature of the column at 55°C,
Add 5 v/v % to the fat and add 55°C warm water to it.

The maltose-rich fraction was collected by flowing at a flow rate of 13, and a high-purity maltose solution of 94.4 w/wx per maltose-containing solid was contaminated.

The high-purity maltose solution collected by performing the above fractionation process 20 times was concentrated under reduced pressure to reduce water content to 4. The crystalline anhydrous α-
2. Maltose per solid substance. Ow/wχ addition,
The mixture was stirred at 110°C for 20 minutes, then passed through a screw-type extrusion granulator to form a granular powder, and transferred to a drying room.
Crystallization and ripening were carried out while drying with hot air at 0°C for 2 hours to obtain a refined anhydrous α-maltose powder containing optical isomer α-maltose [SQ, 2 w/wχ, water content 0.48 w/w Z]. was obtained in a yield of about 93χ based on the high purity maltose of the original V[.

Similar to the anhydrous maltose powder obtained by the method of Reference Example 1, the crystal can be advantageously used as a dehydrating agent for various hydrated substances.

Reference Example 5 95 β-maltose hydrated crystals obtained by the method of Reference Example 1
8A of crystalline anhydrous β-maltose powder with a moisture content of 0.3Q w/wχ was prepared by vacuum drying at ℃ for 2 days.1. Similar to human maltose/AC water powder, fTfl can be used as a dehydrating agent for various hydrated substances.

Reference Example 6 The high purity maltose aqueous solution obtained by the method of Reference Example 3 was diluted with water 2
Concentrate under reduced pressure to 5 w/vχ, then spray from the nozzle from the top of the drying tower with a high-pressure pump, dry with hot air at 160°C, collect at the bottom of the drying tower, take it out of the tower, and remove moisture. A powder of 0.40 w/wχ was obtained.

Is Reference Example 1 used as a seed crystal for this powder? Substantially amorphous anhydrous maltose powder was prepared by mixing approximately 0.1 w/vχ of human-obtained β-maltose hydrate crystals.

Similar to the anhydrous maltose powder obtained by the method of Reference Example 1, the crystal can be used as a dehydrating agent for various hydrated substances.

#Reducible 7 High purity maltose aqueous solution obtained by the method of Reference Example 4 was diluted with water 3
il to 0w/w%! ! Pressure concentration and then spray drying in the same manner as in Reference Example (1) to obtain an amorphous anhydrous maltose powder with a moisture content of 0.45 w/wχ.

Similar to the anhydrous maltose powder prepared by the method of Reference Example 1, quartz can be advantageously used as a dehydrating agent for various hydrated substances.

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

Example 1 Soboro Kaze Gyuhi fQF Gaku 4kg water 6000 rB! Melt it with water, pour it into a wooden frame and heat it for 20 minutes at 100℃.
After steaming for 1 minute, add 8 kg of anhydrous maltose powder obtained by the method of Reference Example 7 and 1 kg of sugar, then add 1 kg of starch syrup, knead thoroughly, and then shape.
The ice crystals were left in a room for 16 hours to convert anhydrous maltose into hydrated β-maltose crystals in the surface layer of the ice crystals, which were then lightly rolled to crack the surface to obtain Soboro-style gyuhi.

The ice crystals had good flavor, were not susceptible to microbial contamination, and maintained high quality over a long period of time.

Ice crystals are easily digested and absorbed, making them suitable as nutritional supplements after illness.

Example 2 Powdered egg yolk Egg yolk prepared from raw eggs was sterilized using a plate-type heat sterilizer for 60 minutes.
After sterilization at ~64°C, 4 parts by weight of the anhydrous maltose powder obtained by the method of Reference Example 6 was mixed with 1 layered part of the obtained liquid egg yolk, transferred to a vat, and left for 2 days to obtain β- A block was prepared by converting the maltose into hydrated crystals. This block was pulverized by a cutting machine and classified to obtain powdered egg yolk.

Ice crystals are used as nutritional supplements such as oral liquid food and tubed liquid food.
It can be used for T profit.

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

Example 3 Powdered medicinal liquor 10g of pullulan was dissolved in 2000+sl of medicinal liquor, and 10kg of anhydrous maltose powder obtained by the method of Reference Example 1 was added to this.
The mixture was mixed, and then block-formed and powdered in the same manner as in Example 2 to obtain a powdered medicinal liquor.

Ice crystals have sufficient medicinal properties and are convenient to carry.

It is also advantageous to use the powder by molding it using a granulating machine or a tablet machine.

Example 4 After mixing 10 kg of powdered butter with 20 kg of anhydrous maltose powder obtained by the method of Reference Example 2 in a mixer, Example 2
In the same manner as above, it was made into blocks and powdered to obtain powdered butter.

Ice crystals can be advantageously used as therapeutic nutrients such as oral liquid diets and tubed liquid diets.

Example 5 Powdered cream After 8 kg of anhydrous maltose powder obtained by the method of Reference Example 3 was mixed with 2 kg of fresh cream, the mixture was formed into blocks and powdered in the same manner as in Example 2 to obtain a powdered cream.

Ice crystals are powdered creams with a good flavor and can be used as nutritional supplements for oral liquid foods, tubed liquid foods, and the like.

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

Example 6 Powdered Yogurt After mixing 2 kg of brain yogurt with 10 kg of anhydrous maltose powder obtained by the method of Reference Example 4, it was made into blocks and powdered in the same manner as in Example 2.
8t.

Ice crystals not only have a good taste, but also can keep lactic acid bacteria alive and stabilized for a long period of time. Therefore, ice crystals can be advantageously used as a live bacterial intestinal control agent and as a therapeutic nutritional agent such as an oral liquid diet or a tube-transferred liquid diet.

Furthermore, it is also possible to advantageously mold this powder with a granulator, 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 anhydrous maltose powder obtained by the method of Reference Example 6 into 500 g of medicinal ginseng extract, it was made into blocks and powdered in the same manner as in Example 2 to obtain a powdered medicinal ginseng extract. Obtained.

Ice crystals contain 111iffi of vitamin B1 and vitamin B
Together with the powdered ginseng powder, it was passed through a granulating machine to obtain vitamin-containing granular medicinal ginseng extract.

Ice crystals can be advantageously used as fatigue-relieving agents, tonics, and obsessives. It can also be used as a hair growth agent.

Example 8 Solid preparation for liquid food 500 parts by weight of anhydrous maltose powder obtained by the method of Reference Example 1, 270 parts by weight of powdered egg yolk obtained by the method of Example 2, 209 parts by weight of skim milk powder, 44 parts by weight of sodium chloride i? H1 Potassium chloride 1.85 parts by weight, 4 parts by weight of magnesium sulfate, 0.01 parts by weight of thiamin, 0.1 parts by weight of sodium ascorbate, 0.6 parts by weight of vitamin E acetate.
heavy ff1815 and nicotinic acid amide 0.0 Jfflf
A formulation consisting of part fi was prepared, and 25 g each of this formulation was filled into moisture-proof laminate sachets and heat-sealed to produce a liquid edible solid formulation.

This solid preparation has a moisture content of 94% in the atmosphere inside the sachet, does not require low-temperature storage, and is stable for a long period of time 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 ml of water to make a single meal, 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 lump that occurred 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 RFP4111340 medium (pl
+7.2) Wash and add approximately 2 x 106/1 to the same medium.
The mixture was suspended at 35°C. After adding partially purified human interferon at a ratio of 20011/ml and keeping it for about 2 hours, Sendai virus was added to it at a rate of about 3
It was added at a rate of 0.00 hemagglutination titer/ml and kept for 20 hours to induce human interferon. This is about 4℃
The precipitate was removed by centrifugation at approximately 1,000 g, the resulting supernatant was further microfiltered, and the filtrate was applied to an antibody column on which an anti-interferon antibody was immobilized according to a known method. After removing the adsorbed fraction, the adsorbed fraction is eluted, and the membrane is compressed to a concentration of approximately 0.01 w/v
, a concentrated solution with a specific activity of about 1.5
A yield of about 4+ml per quarter was obtained.

8 g each of the pyrogen-free anhydrous maltose obtained by the method of Reference Example 5 was placed in a 100 ml moisture-proof plastic bottle, and 0.2 ml (approximately 3 million 1) of the interferon-containing liquid obtained earlier was added to each bottle. A solid preparation for injection was obtained by aseptically sealing the rubber stopper and cap.

This production method dehydrates the interferon-containing liquid by simply dropping it onto the anhydrous maltose powder, so it does not require freeze-drying or other treatments, equipment, or energy, and is also effective in stabilizing interferon. .

Because ice crystals are easily soluble in water, they are used subcutaneously, intramuscularly, and as test reagents, antiviral agents, anti-M1 tumor agents, etc.
It can be advantageously used as an injection into a vein.

The activity of human interferon was measured by a known plaque half-life method using FL cells. Blush F! The agglutination value is J, E, 5alk, The Journal
or Immunology, Volume 49, No. 87-98
(1944).

Example 10 Solid Preparation for Injection After injecting neonatal hamsters with 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. Approximately 15g of Ihl generated under the skin
! After the tumor was excised and cut into small pieces, the cells were suspended in trypsin-containing physiological saline to disperse and separate the cells. These cells were added to human serum 5
Cells were diluted to a concentration of approximately 5xlO6/ml in a medium of the same composition, washed with Eagle's minimal basal medium at pH 7.2 and kept at 37°C containing v/v'
, endotoxin derived from E. coli was added at a rate of approximately 10 μg/ml and maintained for 16 hours to induce and produce T. coli necrosis factor.

This was centrifuged at 4°C and approximately 1,000 g to remove the precipitate, and the resulting supernatant was dialyzed for 21 hours with physiological saline containing OIM phosphate solution, pH 7.2.0. The product was further subjected to microfiltration, a-condensation, and freeze-drying to obtain a powder containing Tsumoa necrosis factor activity. The obtained powder was reported by G. Bodo (Sya+posium on
Preparation, 5 standards
ion and C11nical Use of r
interferon, 11th Interna
tional Immunobiological
Symposium 8 & 9 June 197
7, adsorption/desorption to ion exchanger, gel J & filtration molecular foot fractionation, ie I+? according to Zagreb, Yugoslavia). ! Interferon was then removed by means of microfiltration, and further purified and concentrated by ammonium sulfate salting out and ConΔ-Sepharose affinity chromatography to confirm that it has the ability to cause hemorrhagic necrosis in Meth A sarcoma and has no adverse effects on normal cells. Contains the characteristic high purity Tsumoa Necrosis Factor at a concentration of approximately 0.
．． 01 w/v Z concentrate at a rate of about 3 per 4 hamsters
0ml was obtained. The Tsumoa necrosis factor thus obtained was a glycoprotein having a specific activity of about 3.5×105 U without any contamination with the inducer used.

50 g each of pyrogen-free anhydrous maltose obtained by the method of Reference Example 4 was placed in a glass bottle (ioOa+l capacity), and added to the previously obtained Tsumoa Necrosis
Factor concentrate 0.5ml (approx. 1.75 x 1030
) and aseptically sealed the rubber stopper and cap to obtain a solid preparation for injection.

In this production method, the liquid containing TSUMOA Necrosis Factor is dehydrated to 11< water maltose powder, so it does not require any treatment such as freeze-drying or smoke, but it is also effective in stabilizing the TSUMOA Necrosis Factor. It is.

Since ice crystals are easily soluble in water, they can be advantageously used as anti-inflammatory agents, nutritional supplements, etc., and as d-benefits for intravenous drips.

In addition, the activity of Tsumoa necrosis factor is E,
Pickli3, Lymphok 1nes, Volume 2, pp. 235-272, “Turaor Nec
rosis Factor, 1, 8cadeI
Tumore necrosis factor susceptibility L-9 reported in Ilic Press (1981)
Using 29 cells, the number of surviving cells after culturing for a certain period of time was calculated as (
A known method for determining 411 was used.

Example 11 Ointment for wound treatment To 500 g of anhydrous maltose obtained by the method of Reference Example 7,
Add 50 ml of methanol in which 3 g of iodine has been dissolved, mix, and then add 200 ml of 10 w/v % pullulan water 1δ solution!
was added and mixed, and the mixture was allowed to stand at room temperature overnight to convert into hydrated β-maltose crystals, thereby obtaining an ointment for wound treatment showing appropriate spreadability and adhesion.

Ice crystals can be used to treat injuries such as cuts, abrasions, burns, and ulcers caused by athlete's foot by applying them directly to the wound surface or by applying them to gauze, oiled paper, etc.

In addition, ice crystals not only have a bactericidal effect with iodine, but also act as a nutritional supplement to cells with maltose, which shortens the healing period and allows the wound surface to heal cleanly.

(Effects of the Invention) As is clear from the above, the anhydrous maltose of the present invention can be incorporated into pharmaceuticals such as nutritional supplements and physiologically active substance preparations, their raw materials or processing intermediates, and converted into β-maltose hydrated crystals. The method of manufacturing pharmaceuticals by dehydrating them does not require harsh conditions such as heating and drying, so it does not cause deterioration such as decomposition of active ingredients or decrease in activity, making it easy to produce stable and high-quality pharmaceuticals. can be manufactured.

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

[Brief explanation of drawings]

FIG. 1 shows α-maltose containing ft48. An X-ray diffraction pattern of an amorphous powder with o w/wχ is shown. FIG. 2 shows the X-ray diffraction pattern of a crystalline powder with an α-maltose content of 55.6 w/wχ. FIG. 3 shows an X-ray diffraction pattern of a crystalline powder containing α-maltose at 61.4 w/w%. FIG. 4 shows an X-ray diffraction pattern of a crystalline powder containing α-maltose with MH38,7 w/wχ. Figure 5 shows the α-maltose content? 4.2 w/v:C
The X-ray diffraction pattern of Tearo crystalline powder is shown. FIG. 6 shows the X-ray diffraction pattern of crystalline anhydrous β-maltose powder. Figure 7 shows β-maltose hydrated crystals (maltose 111
111) $5) Shows the X-ray diffraction pattern at the end. Sai 1 Figure turning angle (2 hi) t 2 Figure diffraction angle (2 hi) Sai 3 Prisoner diffraction angle (2ω9 Turning angle (2 + 9) Sai 5 Figure turning front angle (2 (! 4) t6 figure turning angle ( 2 Illusion?!E1 Front angle (:L6)-) Procedural amendment April 2, 1985 1, Name of the case 1985 Patent Application No. 278636 2 Name of the invention Dehydrated pharmaceutical and its manufacturing method 3, Relationship with the case of the person making the amendment Patent applicant 4, Item 5 of “Detailed Description of the Invention” of the specification subject to amendment, Contents of the amendment (+1 “Slightly It can also be heated.'' ``It can be heated slightly or it can also be exposed to a steam atmosphere to accelerate the conversion of the β-maltose hydrated ice crystals and shorten the time.'' (2) "Oil-soluble substance" described in the first line of page 26 of the specification
is corrected to "oil-soluble substances, emulsions, latex, etc." Procedural amendment June 20, 1985 1, Name of the case, Patent Application No. 278636 of 1985 2, Name of the invention Dehydrated pharmaceuticals and their manufacturing method 3, Person making the amendment Relationship with the case Patent applicant 4, Amendment Subject 5, Contents of amendment (11 Statement on page 21, line 2 of the specification “...
···Are better. '', insert the following sentence: ``Cyclodextrins need not be limited to high-purity ones; low-purity cyclodextrins that are difficult to dry and difficult to powder, such as starch syrup-like starches containing a large amount of maltodextrin and various types of sifurobukisu l-IJ. Partial hydrolysates can also be used advantageously.'' (2) ``In addition, anhydrous maltose...impregnated and mixed,'' written in lines 3 to 4 on page 27 of the specification, can be changed to the following sentence: will be corrected. "Anhydrous malt-2?β can also be produced by impregnating or mixing anhydrous maltose with water-containing oil-soluble substances, emulsions, latex, etc.
- Converted into maltose-containing ice crystals," (3) "Stabilizer," written in line 8 of page 27 of the specification, is corrected to "Stabilizer, which is converted into β-maltose-containing ice crystals." Procedural amendment August 18, 1988 Commissioner of the Patent Office Kuro 1) Mr. Akio 1, Name of the case 1985 Patent Application No. 278636 2, Name of the invention Dehydrated medicine and its manufacturing method 3, Person making the amendment Relationship with Patent applicant representative Ken Hayashibara 6th; I/, S1. ．． ．． ．．・7 4. Section 5 of "Detailed Description of the Invention" of the specification to be amended, Contents of the amendment (1) "Japanese encephalitis vaccine," as described on page 17, lines 19-20 of the specification. , measles vaccine, live polio vaccine, smallpox seedlings.'' (2) "Extracts such as licorice extract," written on page 18, lines 11-12 of the specification will be corrected to "extracts, such as licorice extract, viruses." Procedural amendment February 24, 1988 Commissioner of the Patent Office Kuro 1) Akio Yu 1, Name of the case 1985 Patent Application No. 278636 2 Name of the invention Dehydrated medicine and its manufacturing method 3, Amendment? Patent applicant 4, Section 5 of “Detailed Description of the Invention” of the specification subject to amendment, Contents of the amendment (1) Relative humidity... found out.''? , correct as follows. "We have developed a method to completely contain anhydrous maltose and package it in powdered products, such as balm, powdered intestinal preparations, and granular digestive preparations, to extremely reduce the relative humidity inside the container, resulting in high levels of dry foods, powdered foods, etc. It has been found that the quality can be maintained stably for a long period of time.J (2) "No worries.
``There is no need to worry, and adhesion and caking of powdery substances can be completely prevented.'' (3) “Among other things” as stated in page 16, line 18 of the specification?
, correct as follows. ``For dehumidification and drying, it can be used not only to prevent moisture absorption, such as dry nutritional supplements, but also to powdered substances that absorb moisture and easily solidify, such as powdered yeast extract, powdered milk, and powdered yogurt. , powdered cheese,
We are focusing on combining and packaging anhydrous maltose with powdered products such as powdered juice, powdered harp, powdered vitamins, granulated soup, granulated bouillon, fish meal, blood meal, bone meal, powdered lactic acid bacteria, powdered enzyme preparation, and granulated digestive preparation. , it completely reduces the relative humidity inside the packaging container and completely prevents the adhesion and caking of powdery substances, so it is a high quality product with good flowability immediately after production. It can also be used for purposes such as long-term maintenance. Also, water content? In the case of dehydration, for example,

Claims (14)

[Claims] (1) A dehydrated pharmaceutical product in which anhydrous maltose is contained in a pharmaceutical product, its raw material, or a processing intermediate and converted into β-maltose hydrated crystals. (2) The dehydrated pharmaceutical according to claim (1), wherein the anhydrous maltose is high purity maltose containing 85 w/w% or more of maltose per solid substance. (3) The dehydrated pharmaceutical according to claim (1) or (2), wherein the anhydrous maltose is a powder. (4) The dehydrated pharmaceutical according to claim (1), (2) or (3), wherein the anhydrous maltose has a water content of less than 3 w/w%. (5) Anhydrous maltose is crystalline anhydrous α-maltose,
Claims (1) and (1) are crystalline anhydrous β-maltose or amorphous anhydrous maltose.
Dehydrated pharmaceuticals according to 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. Dehydrated pharmaceuticals according to paragraph (4) or paragraph (5). (7) Claim No. (1) characterized in that the dehydrated drug is a drug used orally or parenterally.
- Dehydrated pharmaceuticals described in (6). (8) A method for producing a dehydrated pharmaceutical product, which comprises adding anhydrous maltose to the pharmaceutical product, its raw materials, or processing intermediates and converting it into hydrated β-maltose crystals. (9) The method for producing a dehydrated pharmaceutical according to claim (8), wherein the anhydrous maltose is high purity maltose containing 85 w/w% or more of maltose per solid substance. (10) The method for producing a dehydrated pharmaceutical according to claim (8) or (9), wherein the anhydrous maltose is a powder. (11) Claims (8) and (9) characterized in that the anhydrous maltose has a water content of less than 3 w/w%.
A method for producing a dehydrated pharmaceutical according to paragraph or paragraph (10). (12) Claims (8), (9), and (12) characterized in that the anhydrous maltose is crystalline anhydrous α-maltose, crystalline anhydrous β-maltose, or amorphous anhydrous maltose. The method for producing a dehydrated pharmaceutical according to item (10) or item (11). (13) Claims (8), (9), and (10) characterized in that the dehydrated pharmaceutical contains gelatinized starch, alcohol, an oil-soluble substance, or a physiologically active substance. A method for producing a dehydrated pharmaceutical according to paragraph (11) or paragraph (12). (14) Claim No. 8, characterized in that the dehydrated drug is a drug used orally or parenterally.
) to (13).