JP2003095987A - Volatilization/sublimation inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a volatilization/sublimation inhibitor for sublimable matter effectively and stably usable in a wide range of solid preparations, imparting the solid preparations with good properties, in particular effective for preventing whickers problematic in pharmaceutical preparations, foods, and the like. SOLUTION: This volatilization/sublimation inhibitor is based on the finding that a yeast cell wall fraction consisting of microbial cell residues obtained by removing soluble intracellular components from enzyme-treated yeast has good gas-barrier tendency and volatilization/sublimation inhibitory effect on sublimable matter. thus, this inhibitor to be used consists of the above residues, or the residues obtained by treating the above residues with an acidic aqueous solution to further remove solubilized components, or is obtained by incorporating a plasticizer and an oxygen barrier tendency-improving agent in either of the former or later residues mentioned above.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a pharmaceutical preparation, a food,
Volatile or sublimable substances contained in solid preparations of food materials, food additives, agricultural chemicals, or flavors, etc. Volatile or sublimation inhibitors for substances, for example, for the prevention of whiskers which are a problem in pharmaceutical preparations, foods, etc. The present invention relates to an agent for volatilization or sublimation of a volatile or sublimable substance, a method for preventing volatilization or sublimation thereof, and a treated product for preventing volatilization or sublimation thereof.

[0002]

2. Description of the Related Art Generally, in solid preparations of various fields such as pharmaceutical preparations, foods, food materials, food additives, agricultural chemicals, and flavors, when the product contains a volatile or sublimable substance, its volatilization Alternatively, sublimation causes a problem that the quality of the product is changed and the value of the product is reduced. Especially, in the field of pharmaceutical preparations and foods, when solid preparations contain sublimable components, the sublimable components volatilize to precipitate and grow crystals, forming crystals called whiskers (whisker crystals). This causes a problem of deteriorating the quality of the product.

[0003] In pharmaceuticals, foods, etc., generally, substances that easily form whiskers include menthols, benzoic acids, salicylic acids, carbamazepine, etenzamid, caffeines and the like, which are mixed in solid preparations. Due to their sublimability, these substances easily sublime on the surface of the preparation or around the storage container during storage to form whiskers. In solid preparations such as powders and granules containing such substances, whisker needle-like crystals deposited on the surface aggregate, resulting in poor fluidity and change in drug content, making it impossible to establish a prescription formulation. Problems such as occur. In addition, whiskers made of these powders, granules, and tablets are apt to be mistaken as mold by consumers, which is a quality problem in appearance.

Various methods have heretofore been proposed in order to prevent the generation of whiskers due to such sublimable substances. For example, a method of coating a sugar coating on the surface of the preparation with a sufficient thickness, a method of film coating with a coating agent containing a polymer, or a method of preventing the sublimation phenomenon by mixing a sublimable drug and an adsorbent is proposed. Has been done. A specific example is "Pharmaceutical magazine" 96 (10) 12.
23-1227 (1979), sublimable caffeine-containing preparations or beard crystal-forming drug-containing preparations and charcoal,
A method of coexisting silicic acid anhydride and / or montmorillonite without mixing and a method of blending caffeine and activated carbon or bentonite are described in "Pharmaceutical Science" 41
(3) 161-171 (1981), white caffeine anhydrous or white alundum or light anhydrous silicic acid (Aero
Each method of mixing sil 200) has been reported.

Further, Japanese Patent Laid-Open No. 61-129138 discloses a method of coating a sublimable drug with a coating agent containing cyclodextrins, and Japanese Patent Publication No. 56-53525 discloses a sublimable drug and an adsorbent. Each of the methods of simultaneously blending is disclosed. Furthermore, as a method by adding a drug,
JP-A-2-85214 discloses a method of blending an antacid, and JP-B-5-38733 discloses a blending method of β-1,4 glucan powder. JP-A-5-339158.
JP-A-8-301764 describes a method of blending hydrous silicon dioxide, and JP-A-8-301764 describes a method of blending one or more kinds selected from an antacid and silicon dioxide.
Japanese Patent No. 310953 discloses a method of blending glycyrrhizic acid or a salt thereof into a material containing plastic aluminum, and Japanese Patent Laid-Open No. 2000-247870 discloses a method of blending polyvinylpyrrolidones. ing.

[0006] However, for example, coating with a coating agent has a drawback that the manufacturing cost is high, a tablet becomes large due to the coating, or a coating which delays the disintegration is used for a drug which requires rapid disintegration. On the other hand, the efficacy of the drug became negative, and it was difficult to obtain an ideal coating. Also, in the case of using other methods, for example, in the method using an adsorbent, the adsorbent retains the drug, so that the absorption of the drug into the living body is inhibited, or in the method using an antacid, The basic substance for the acid may change the active ingredient in the solid preparation and may not be effective enough to prevent it, effectively preventing the precipitation of crystals due to sublimation in a wide range of solid preparations. It left a problem that it was difficult to do.

[0007]

DISCLOSURE OF THE INVENTION The present invention is a volatile or sublimable substance which can be effectively and stably used in a wide range of solid preparations, and further imparts good properties to the solid preparations. Volatile or sublimation inhibitors, especially pharmaceutical formulations,
The present invention relates to a volatile or sublimation-preventing agent for a volatile or sublimable substance for the prevention of whiskers, which is a problem in foods, etc., a method for preventing the volatilization or sublimation thereof, and a solid preparation-treated product for preventing the volatilization or sublimation.

[0008]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that a yeast cell wall fraction consisting of bacterial cell residues obtained by removing soluble intracellular components from an enzyme-treated yeast is excellent. The present invention was made by discovering that it has a gas barrier property and has an effect of preventing volatilization or sublimation of a volatile or sublimable substance. In particular, the yeast cell wall fraction of the present invention has an excellent effect in preventing whiskers, which are a problem in pharmaceutical preparations, foods, etc., and can be used as a wide range of volatilization or sublimation inhibitors from the property of yeast cell walls. It has an excellent effect as a volatilization or sublimation inhibitor for solid preparations, that is, it gives good properties to solid preparations such as binding and disintegration of preparations when used in solid preparations. . As the yeast cell wall fraction of the present invention, a microbial cell residue obtained by removing soluble intracellular components from the enzyme-treated yeast, and a solubilized component obtained by treating the bacterial cell residues obtained by removing the soluble intracellular components with an acidic aqueous solution, Residues removed, and powdered water dispersions of these microbial cell residues from which soluble soluble intracellular components were removed, and those in which a plasticizer was added to the yeast cell wall fraction, further sugars, low hygroscopic amino acids It is possible to use those to which an oxygen barrier property improving agent such as inorganic salts forming polyhydrates, polyhydrates, low hygroscopic sugar alcohols, etc. is added.

That is, the present invention is characterized by comprising a yeast cell wall fraction consisting of bacterial cell residues obtained by removing soluble intracellular components from enzyme-treated yeast, or a yeast cell wall fraction to which a plasticizer has been added. Or a sublimation substance volatilization or sublimation inhibitor (claim 1), the yeast cell wall fraction according to claim 1 or the yeast cell wall fraction to which a plasticizer is added,
A volatile or sublimable substance volatilization or sublimation inhibitor characterized by being further added with an oxygen barrier property improving agent (Claim 2), and the oxygen barrier property improving agent is a monosaccharide, an oligosaccharide, or a low hygroscopic agent. 1 of the group selected from water-soluble amino acids, inorganic salts forming polyhydrates, and sugar alcohols with low hygroscopicity
Or a compound of two or more species, wherein the volatile or sublimation inhibitor of the volatile or sublimable substance according to claim 2 (claim 3) or the yeast cell wall fraction is soluble in the enzyme-treated yeast. Prevention of volatilization or sublimation of the volatile or sublimable substance according to any one of claims 1 to 3, wherein the microbial cell residue from which internal components have been removed is treated with an acidic aqueous solution to further remove solubilized components. Prevention of volatilization or sublimation of the agent (Claim 4) or volatilization or sublimation of the volatile or sublimable substance is prevention of whisker generation, prevention of volatilization or sublimation of the volatile or sublimable substance according to any one of claims 1 to 4. Agent (Claim 5)
Or, the prevention of volatilization or sublimation, pharmaceutical formulations, foods, food materials,
Volatilization or sublimation of a volatile or sublimable substance contained in a solid preparation of a food additive, a pesticide, or a flavoring agent is prevented, or volatilization of a volatile or sublimable substance according to any one of claims 1 to 5, It consists of a sublimation inhibitor (claim 6).

In the present invention, a volatile or sublimable substance, or a substance containing the volatile or sublimable substance is treated with the volatile or sublimation inhibitor according to any one of claims 1 to 6, which is characterized in that a solid formulation is volatilized or sublimated. Method for preventing volatilization or sublimation of a volatile substance or a substance containing the same (claim 7), or a solid preparation having a volatilization or sublimation prevention property characterized by being treated by the method for preventing volatilization or sublimation of claim 7, or a method thereof Consists of inclusions (claim 8).

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a microbial cell residue obtained by removing soluble intracellular components from an enzyme-treated yeast, and a solubilized component obtained by treating the bacterial cell residue obtained by removing the soluble intracellular components with an acidic aqueous solution. Residue removed, and those obtained by pulverizing the aqueous dispersion of microbial cell residue from which these soluble intracellular components have been removed, and those with a plasticizer added to the yeast cell wall fraction, further sugars, low hygroscopicity Amino acids, inorganic salts forming polyhydrates, those with added oxygen barrier property improving agent consisting of low hygroscopic sugar alcohols, etc. are used as a volatilization or sublimation inhibitor for volatile or sublimable substances. Become. The volatile or sublimation inhibitor of the volatile or sublimable substance of the present invention is used for preventing the volatilization or sublimation of the volatile or sublimable substance contained in the pharmaceutical preparation, food, food material, food additive, pesticide, or solid preparation of flavor. It is used, and particularly has an excellent effect in preventing whiskers which are a problem in pharmaceutical preparations, foods and the like.

The volatilization or sublimation inhibitor of the present invention can be used as a wide range of volatilization or sublimation inhibitor due to the property of yeast cell wall, and when it is used in a solid preparation, it is It exhibits good physical properties as a solid preparation in terms of binding properties and disintegration when the preparation is used, and has a practically excellent effect as a volatilization or sublimation inhibitor for the solid preparation. As a method of applying the volatilization or sublimation inhibitor of the present invention in the production of a solid preparation, basically, a volatile or sublimable substance is covered with the volatilization or sublimation inhibitor of the present invention to form a shield from the outside. Any suitable formulation means generally used in this field such as mixing and coating can be used. The preparation of the volatile or sublimation inhibitor of the present invention and the solid preparation using the same will be described in detail below.

(Raw material yeast) As the raw material of the coating agent of the present invention, any yeast can be used as long as it belongs to taxonomically-classified yeasts. For example, brewer's yeast, wine yeast and baker's yeast. , Torula yeast, and more specifically, more specifically, Saccharomyces cerevisia of the genus Saccharomyces.
e), Saccharomyces rou
xii), Saccharomyces carlsbergensis (Sac
charomyces carlsbergensis), Candida utilis, Candida tropicalis, Candida lipolytica, Candida flaveri, and the like.

These yeasts can be used alone or in combination. It is preferable to use live yeast as the yeast, but even when yeast other than live yeast such as dried yeast is used, it can be suspended in water or the like and treated in the same manner as live yeast. Furthermore, the shape and size of the yeast used is not particularly limited,
The shape is preferably as close to a spherical shape as possible, and the size thereof is preferably in the range of 1 to 20 μm.

(Yeast Cell Wall Fraction) Yeast contains intracellular components soluble in water or polar solvents, such as proteins, amino acids, sugars, nucleic acids, and organic acids. Is easily solubilized in water, and when it is used as a coating agent without removing these soluble intracellular components, not only the effect of delaying the elution start time is hindered but also the coating power is deteriorated. Therefore, in order to obtain a coating agent having the effect of delaying the elution start time, it is essential to use the yeast cell wall fraction after removing these soluble intracellular components from the yeast.

In order to remove these soluble intracellular components from yeast to obtain a yeast cell wall fraction, it is necessary to solubilize these intracellular components by enzymatic treatment and remove them outside the bacterial cells. Then, as the enzyme treatment, a so-called auto-digestion method using an enzyme in yeast cells, an enzyme addition method of adding an enzyme such as protease, nuclease, β-glucanase, esterase, lipase or the like from the outside, or a method using them in combination Etc., as long as they are methods used when producing yeast intracellular components as yeast extract,
Any enzyme treatment method can be used. From this, as the yeast cell wall fraction in the present invention, the yeast extract extraction residue in the known production of yeast extract can be advantageously used. In addition, for the purpose of rapidly performing enzyme treatment, prior to enzyme treatment of yeast, pretreatment involving physical disruption of cell wall by a high-pressure homogenizer or the like may be performed. When using this high-pressure homogenizer, for example, It is preferable to disperse under a pressure of 100 to 1000 kg / cm ² .

The yeast which has been subjected to the enzyme treatment is subjected to a treatment for removing soluble intracellular components such as centrifugation,
A yeast cell wall fraction is obtained as the bacterial cell residue. As described above, the yeast cell wall fraction obtained without any particular chemical treatment is composed of a glucan, mannan, and chitin layer, which is a physically and chemically relatively strong film, and thus has a protective function for the encapsulated substance. A large amount of substance can be included without damaging it, and it can be used as an excellent coating agent, but if necessary, yeast washing treatment, pH
-The yeast cell wall fraction can also be prepared by incorporating a temperature / pressure adjustment treatment or the like.

(Acid-treated yeast cell wall fraction) Next, the acid-treated yeast cell wall fraction is obtained by treating the yeast cell wall fraction obtained by removing soluble intracellular components by enzymatic treatment of yeast with an acidic aqueous solution. The yeast cell wall fraction can be prepared as a yeast cell residue from which the solubilized components have been removed. More specifically, the yeast cell wall fraction can be 0.01 to 2N, preferably 0.1.
Prepared by treating with ~ 0.5N acid such as hydrochloric acid, sulfuric acid, nitric acid, etc., separating the suspension into supernatant and yeast cell residue by centrifugation and collecting the yeast cell residue. can do. In addition, it is preferable to heat the acid treatment to about 80 ° C.

Since the acid-treated yeast cell wall fraction also comprises a chemically relatively strong film composed of a glucan, mannan and chitin layer, it encloses a larger amount of the substance without impairing the protective function of the encapsulating substance. Besides being able to
The yeast cell wall fraction can control the elution start time by changing the concentration of the acidic water used when treating the bacterial cell residue obtained by removing soluble bacterial cell components from the enzyme-treated yeast with an acidic solution. It can be used as an enteric coating agent or the like.

(Plasticizer added to yeast cell wall fraction) In the present invention, the yeast cell wall fraction and the acid-treated yeast cell wall fraction have excellent effects even if they are used as they are, but the volatility of the volatilization or sublimation inhibitor is low. It is preferable to use a plasticizer for the purpose of improving the water resistance and the like. These plasticizers include
In the food field, glycerin, sorbitol, amino acids, organic acids, monoglycerides, diglycerides,
Examples thereof include triglycerides and fats and oils centering on MCT. Further, in the pharmaceutical field, plasticizers which are acceptable as pharmaceutical additives such as triacetin, triethyl citrate, and acetylated monoglyceride can be mentioned.

(Oxygen Barrier Property Improver Added to Yeast Cell Wall Fraction) The volatile or sublimation inhibitor of the present invention may contain an oxygen barrier property improver in order to further improve the oxygen barrier property. The oxygen barrier improving agent is not particularly limited, but when used in foods or pharmaceutical preparations, those comprising an edible substance are preferable, and specifically, monosaccharides (eg glucose, mannose, etc.) and oligosaccharides. (For example, maltose, trehalose, fructose, arabinose, nigerooligosaccharides, lactose, D-
Sugars with short chain length such as glucono-1.5-lactone, amino acids with low hygroscopicity (eg, arginine hydrochloride), inorganic salts forming polyhydrate (eg, ferrous sulfate, diphosphate) Sodium hydrogen, etc.), sugar alcohols having low hygroscopicity (eg, palatinit, vitamin C, etc.) and the like. These oxygen barrier property improving agents may be used in combination of two or more kinds. Further, the addition amount of the oxygen barrier property improving agent is such that the volatilization or sublimation inhibitor of the present invention, the film formed from the volatilization or sublimation inhibitor, the characteristics of the packaging material composed of the film, particularly under high humidity (RH 60%, 23
Oxygen permeability coefficient (cm ³ · mm / m ² · atm)
-24 hr) It can be appropriately selected within a range capable of achieving less than 0.1. Furthermore, the oxygen permeability coefficient can be controlled by appropriately selecting the type of oxygen barrier property improving agent, the concentration used, and the like.

(Production of Solid Formulation Using Volatile or Sublimation Inhibitor) When producing a solid formulation using the volatilization or sublimation inhibitor of the present invention, basically, a volatile or sublimable substance is
It is not particularly limited as long as it is covered with the volatilization or sublimation inhibitor of the present invention and forms a shield against the outside, but is not particularly limited.
Usually, an appropriate solid formulation preparation means used in this field such as mixing and coating can be used. For example, using the volatile or sublimation inhibitor of the present invention,
To prepare a solid preparation such as a pharmaceutical preparation, the volatile or sublimation inhibitor of the present invention is mixed with various excipients, additives, lubricants, etc. together with the volatile or sublimable active ingredient, and this is prepared. It can be granulated by a granulation method such as a wet or dry granulation method or a direct powder compression method, and can be formed into a solid preparation such as granules or tablets. When the volatile or sublimation-preventing agent of the present invention is coated for formulation, granules obtained by blending an active ingredient with an excipient or other compounding agent, and tablets are treated with a whisker inhibitor. It can be coated by a coating means commonly used in this field to prepare a preparation.

(Physical properties when the volatilization or sublimation inhibitor of the present invention is formulated by coating) The method of formulating by coating using the volatilization or sublimation inhibitor of the present invention is particularly effective for preventing whiskers and the like from occurring. It is valid. The coating using the volatile or sublimation inhibitor of the present invention, compared with the conventional edible coating, has a non-sticky finish for the viscosity, and there is no adhesion of particles after coating, and further elution start time It has excellent physical properties that it can be used as a controllable enteric coating agent or a bitterness masking agent. Further, the coating layer (film) of the coating agent of the present invention has extremely low gas permeability of oxygen and the like and moisture permeability, and is particularly excellent among existing edible films, and it is used in a wide range of fields such as food, pharmaceuticals, feed and agriculture. Can be applied to.

As the conventional coating agent solution, a semi-viscous fluid in which a high molecular polymer is dissolved or a dilatant fluid such as an aqueous suspension of starch is used. The coating using the sublimation inhibitor can be a plastic fluid and is different from the conventional one in terms of physical properties. Further, since the whisker prevention agent = coating agent itself of the present invention does not have a special medicinal effect, unlike the case where a medicinal component such as an antacid is blended, it does not affect the desired medicinal effect, There is no loss of sex. Further, although it is known that conventional coatings deteriorate the disintegration property when they are coated, the product of the present invention has no effect on the disintegration property, and no denaturation in the preparation due to an interaction with the encapsulating substance is observed.

(Incorporated Substance in Solid Preparation) In the present invention, the volatile or sublimable substance in the solid preparation for the purpose of preventing volatilization or sublimation includes pharmaceutical preparations, foods, food materials, food additives,
A variety of substances that are volatile or sublimable at room temperature contained in solid formulations of pesticides or fragrances are envisioned, but as substances that are particularly targeted in preventing the occurrence of whiskers, the following substances are listed. . That is, as a substance that causes sublimation at room temperature, for example, caffeine (monohydrate), anhydrous caffeine, caffeine citrate, caffeine such as sodium benzoate caffeine, salicylic acid, aspirin, acetaminophen, etenzamid, Chlorpheniramine maleate, tipepidine hibenzate, noscapine, carbetapentane citrate, potassium guaiacol sulfonate, ephedra as a herbal extract, cinnamon syrup, earth dragon,
Extracts such as carrots, licorice, sycamore,
With Kampo extract, the respective extracts such as Kakkonto, Shojikuto, Shoseiryuto, Shikokeishito, and menthols such as 1-menthol, d-menthol, and dl-menthol, for example, ethyl benzoate, phenyl benzoate, Propyl benzoate,
Benzoic acids such as benzyl benzoate, methyl benzoate, sodium benzoate and the like can be mentioned.

(Coating of a solid preparation with a volatilization or sublimation inhibitor) Especially, for the purpose of preventing whiskers,
The coating using the volatile or sublimation inhibitor of the present invention,
The above encapsulating substances alone or in combination, fine particles,
This can be carried out by forming a granulated product having an appropriate particle size such as granules or tablets, and coating this with the volatile or sublimation inhibitor of the present invention suspended in water or a mixed solution of water and a solvent. Specifically, it is carried out by spray-coating the substance to be encapsulated with the suspension of the volatile or sublimation inhibitor of the present invention using a coating machine such as Doria Coater (manufactured by Paulec Co., Ltd.). Any method or apparatus can be used as long as it is a coating method or a known coating apparatus.

The drying temperature in the coating step, that is, the drying temperature after coating the encapsulated substance with the suspension of the volatilization or sublimation inhibitor of the present invention is not particularly limited, but it is usually dried at a temperature of 60 to 90 ° C. The drying temperature can be set according to the temperature stability of the encapsulated substance. Further, by extending the drying time, it is possible to obtain the same effect as the curing effect in the latex type coating agent used as a pharmaceutical additive. Also, the coating amount can be appropriately set according to the amount of the encapsulated substance used, the required application, and the like.

[0028]

The present invention will be described in detail below with reference to examples, but the technical scope of the present invention is not limited to these examples. The weights of yeast cells shown in the examples are all weights (dry weight) in the actual state. Example 1 Beer yeast slurry as a by-product was obtained from a beer factory, and raw mud yeast obtained by centrifugation at 4500 rpm for 10 minutes was suspended in water so that the solid content was 5% by weight. It became cloudy. This suspension was self-digested under reaction conditions of 50 ° C. for 17 hours, and then centrifuged again to obtain a self-digestion residue from which soluble intracellular components were removed as a yeast cell wall fraction. Next, the solid content was suspended in 0.5N hydrochloric acid so that the solid content became 5%, and treated with acid at 80 ° C. for 20 minutes, and then 4500 rp.
Centrifugation under conditions of m, 15 minutes, the solubilized portion was removed, and the resulting residue was used as an acid-treated yeast cell wall fraction (Invention product AY
C). Next, a solution was prepared in which 5% of the coating solution was the above fraction, glycerin was 0.35%, and the remainder was purified water.

Next, as an inclusion substance, aspirin 74.2
6 mg, magnesium aluminometasilicate 74.26
mg, magnesium stearate 1.48 mg (total 150 mg / tablet) was prepared in advance, and the coating liquid was applied to this tablet using a high coater (manufactured by Freund Sangyo Co., Ltd.) to obtain a coating rate of 5%. When spray coating was carried out to 10%, 15% and 20% (tablet weight ratio), good coated tablets could be obtained without peeling of the coating agent.
The coated tablets thus obtained were placed in a container having a volume of 30 ml, 50 tablets having each coating rate and sealed, and then allowed to stand in a constant temperature bath at 60 ° C. for 14 days. 14 days later, the obtained whiskers were scraped off with a brush, dissolved in ethanol, filtered,
The absorbance (λmax 305 nm) was measured with a spectrophotometer, and the amount of whiskers was calculated from the calibration curve of a salicylic acid solution of known concentration. No whiskers were generated in the coating of the product of the present invention, and no change in the coating surface was observed even by observation with a scanning electron microscope.

Comparative Example 1 A commercially available coating agent was used as HPMC (TC manufactured by Shin-Etsu Chemical Co., Ltd.
As 5), a solution having a concentration of 5% was prepared as a coating solution, and then the same test as in Example 1 was performed. The results are shown in Table 1.
Shown in. Generation of whiskers was observed at a coating rate of 5%. In order to suppress whiskers with HPMC, a coating rate of 10% or more is necessary, and it is clear that the coating efficiency is poor. The generation of whiskers in the case of using the product (AYC) of the present invention and the commercially available coating agent HPMC shown in the above example is shown in FIG.
The results of (tablets) are shown in Table 1.

[0031]

[Table 1]

[0032]

The yeast cell wall fraction of the present invention has an excellent gas barrier property, and the volatile or sublimation inhibitor of the present invention is a solid preparation of a pharmaceutical preparation, food, food material, food additive, pesticide, or flavoring agent. It can be effectively used to prevent volatilization or sublimation of various substances contained in the above, which are volatile or sublimable at room temperature.
In particular, it has an excellent effect in preventing whiskers, which are a problem in pharmaceutical preparations, foods, etc., and has outstanding utility in the formulation of solid preparations in these fields. Furthermore, the volatilization or sublimation inhibitor of the present invention can be used as a wide range of volatilization or sublimation inhibitors due to the property of yeast cell wall, and when used in a solid preparation, it further evaporates or sublimes the solid preparation. It has an excellent effect as an inhibitor.

[Brief description of drawings]

FIG. 1 Inventive product (AYC) and commercially available coating agent H
It is a figure which shows the generation condition of a whisker when PMC is used.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 47/26 A61K 47/26 (72) Inventor Norihiro Eguchi 3 Miyahara-cho, Takasaki-shi, Gunma Kirin Kiryu Co., Ltd. F-term in Applied Development Center (reference) 4B018 MC04 MD81 ME14 MF01 4B021 MC10 MK06 MP10 4C076 AA31 AA36 BB01 DD22 DD51 DD67 EE30 EE56 FF39 FF63

Claims (8)

[Claims] 1. A volatilizing or subliming agent, which comprises a yeast cell wall fraction consisting of bacterial cell residues obtained by removing soluble intracellular components from enzyme-treated yeast, or a yeast cell wall fraction to which a plasticizer is added. Anti-volatile or sublimation agent for substances. 2. A volatile or sublimable composition, which comprises the yeast cell wall fraction according to claim 1 or the yeast cell wall fraction to which a plasticizer is added, and an oxygen barrier property improving agent is further added. Anti-volatile or sublimation agent for substances. 3. The oxygen barrier property improving agent is one of a group selected from monosaccharides, oligosaccharides, low hygroscopic amino acids, inorganic salts forming polyhydrates, and low hygroscopic sugar alcohols, or The volatile or sublimation inhibitor for a volatile or sublimable substance according to claim 2, which is a compound of two or more kinds. 4. The yeast cell wall fraction is characterized by being a residue obtained by treating a yeast cell residue obtained by removing soluble intracellular components from enzyme-treated yeast with an acidic aqueous solution and further removing solubilized components. A volatile or sublimation inhibitor for a volatile or sublimable substance according to any one of 1 to 3. 5. The volatilization or sublimation inhibitor for a volatile or sublimable substance according to claim 1, wherein the volatilization or sublimation of the volatile or sublimable substance is prevented by whiskers. 6. A method for preventing volatilization or sublimation of a pharmaceutical preparation, food,
6. A volatile or sublimable substance according to any one of claims 1 to 5, which is used for preventing volatilization or sublimation of a volatile or sublimable substance contained in a solid preparation of a food material, a food additive, an agricultural chemical, or a flavoring agent. Volatile or sublimation inhibitor. 7. A volatile or sublimable substance or a substance containing the volatile or sublimable substance in a solid preparation, which is treated with the volatile or sublimation inhibitor according to claim 1. A method for preventing volatilization or sublimation of the inclusion. 8. A solid preparation having the property of preventing volatilization or sublimation, which is treated by the method of preventing volatilization or sublimation according to claim 7, or a content thereof.