JP2640717B2 - Drug indication composition and drug indication drug carrier - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a drug indication composition, and more particularly, to a color-forming drug composition in which the residual effect of a volatile drug and its end point can be visually recognized by a change in color. The present invention relates to a drug-effect-indicating drug carrier obtained by impregnating, applying or holding the carrier with the color-forming drug composition.

[0002]

2. Description of the Related Art Conventionally, as a preparation in which the end point of a volatile drug can be visually recognized by a change in color tone, Japanese Patent Application Laid-Open No.
No. 51101. This is an oil-soluble room-temperature volatile insecticide and a binder, a water or alcohol-soluble basic or acid indicator as a coloring agent, and a water-soluble basic or acidic agent as an auxiliary colorant with an oil solvent. The present invention relates to a volatile insect repellent sheet with an indicator, which is kneaded with intervening and coated on paper, nonwoven fabric or resin film. The water and alcohol soluble basic or acid indicators used for this indicator are phenolphthalein, thymol blue, alizarin yellow, cresol red, etc., and these indicators are one of the chemical analyses. In ( ² ), it is frequently used as a pH indicator for easily measuring the hydrogen ion concentration [H ⁺ ] ([] means the concentration) in an aqueous solution.

[0003] To describe this coloring mechanism, indicator generally weak organic acids Kayowa bases in depending on the pH of the solution hydrogen ions (protons H ⁺⁾ and hydroxide ion (OH ^-) or added, or eliminated And the color changes. Since the value of [H ⁺ ] is small, it is represented by the value of pH = −log [H ⁺ ], and is measured with a test paper or pH meter soaked with a pH indicator. For example, phenolphthalein is a colorless weak acid [HIn]
It is represented by The aqueous solution is slightly ionized and the conjugate base [In ⁻ ] turns red.

[0004]

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In such an indicator, the visible In
^- (an In stands for the indicator) is determined by the concentration of. If [H ⁺ ] of the solution decreases (the pH value increases), [In ⁻ ] increases to give a red color, and [H ⁺ ] increases (the pH value decreases).
Then, [HIn] increases and becomes colorless. The color change range of phenolphthalein is red at pH 8.3 to 11.0, but becomes colorless if it is smaller than 8.3 and the basicity becomes 11
If it increases more, the structure changes and it becomes colorless. (Under formula)

[0006]

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In the above publication, the water-soluble powder auxiliary colorant is described as being kneaded on a sheet in a dispersed state as a powder in a binder, but as described above, phenolphthalein is used as an indicator. When used, if the concentration of the basic substance is high, it becomes colorless, so that it does not serve as an indicator.

[0008] Aside from that, as described in the official gazette, this indicator shows that the oil-soluble normal-temperature volatile insect repellent prevents the absorption of moisture in the air (in other words, acts as a water repellent). After the insect repellent has volatilized, it absorbs moisture in the air and develops color. In any case, the presence of moisture is an essential condition.

As described above, the indicator disclosed in Japanese Patent Application Laid-Open No. 60-51101 requires the presence of moisture, and the action of the indicator depends on the humidity in the air because the moisture is supplied from the air. At the same time, the page 2 lower right column, page 12 to 14 of the publication states, "After completely repelling the insect repellent, the sheet was left in an environment of 40 ° C and 60% humidity, and the surface was red for about 24 hours. It takes a full day to develop the color even in an environment with a very high humidity of 60%, as described in the above.

[0010]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to show a change in the color tone during the useful life of volatile chemicals such as insecticides, fungicides, and fragrances, that is, in the process of volatilization of the chemicals. It is an object of the present invention to provide a color-forming drug-effect indicating composition capable of accurately and sharply recognizing a remaining state and an end point of a drug effect without being influenced by humidity in the air. Another object of the present invention is to provide a drug-effect-indicating drug carrier which holds a drug-effect-indicating composition having the above-mentioned properties and is stable even in a distribution process.

[0011]

In order to achieve the above object, a drug-indicating composition according to the present invention comprises a non-aqueous volatile agent having various medicinal effects, a non-aqueous volatile solvent, and a non-aqueous system. The four components of a color-forming organic compound having a donating property and a developer having a non-aqueous and electron-accepting property are essential components, and the non-aqueous volatile agent and the non-aqueous volatile solvent have the same volatility. Yes, and both or both of the drug and the solvent are desensitizing , and the volatile drug and the
With the volatile solvent, when it volatilizes and the residual rate decreases,
The reaction between the color-forming organic compound and the color developer starts and is presented.
It is designed to create color .

In addition, the drug-effect-indicating drug carrier according to the present invention comprises a non-aqueous volatile drug, a non-aqueous volatile solvent, a non-aqueous color-forming organic compound having an electron donating property, The essential components are the four components of the developer that has electron-accepting properties.
The non-aqueous volatile agent and the non-aqueous volatile solvent have the same volatility, and both or one of the agent and the solvent are desensitizing , and
The volatile drug and the volatile solvent are volatilized and remain
Is low, the color developing organic compound and the developer
The medicinal-effect-indicating composition, which initiates the reaction to generate color, is impregnated, coated or held on a support such as pulp, paper, cloth, or an organic polymer compound.

[0013]

The color developing mechanism and the function of displaying the efficacy of the composition for indicating efficacy of the present invention will be described. As the non-aqueous color-forming organic compound having an electron donating property, those generally referred to as heat-sensitive dyes belong to this group. There are various types of dyes produced on an industrial scale, such as triphenylmethane-phthalide, fluoran, and phenothiazine-based dyes.One example is triphenylmethane-phthalide-based dye crystal bioreductolactone. The principle of color development of (CVL) will be briefly described. First, the reaction mechanism of this dye with a color developer and a desensitizer is as follows.

[0014]

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Crystal violet lactone itself is colorless, but the lactone ring in the crystal violet lactone is opened by the action of a developer (for example, bisphenol A) to become crystal violet and exhibit blue color. On the other hand, desensitizers (eg, esters, amides, etc.)
When the acid acts, the reverse reaction proceeds and returns to the lactone ring to become colorless.

The drug-indicating composition of the present invention is an application of the color-forming principle to a drug-effect display, and comprises the above-mentioned non-aqueous color-forming organic compound having an electron donating property and a non-aqueous electron-accepting compound. There is a developer, a non-aqueous volatile agent and a non-aqueous volatile solvent (a non-aqueous volatile agent and a non-aqueous volatile solvent are
The presence of the four components (both or either one of which has desensitization) allows the desensitizing effect of the drug and / or solvent to be apparent before volatilization, that is, while the drug and solvent remain sufficiently. Outweighs the action of colorants and reduces color development.

When the above-mentioned chemicals and solvents volatilize and the residual ratio decreases, the reaction between the color developer and the electron-donating color-forming organic compound starts, the color starts to be formed, and the chemicals and / or the solvent are completely removed. When the organic compound no longer remains after volatilization, it exhibits a color tone unique to the electron-donating color-forming organic compound. In this case, if the volatility of the drug and the solvent is of the same volatility, the reaction process and the volatilization process of the volatile drug correspond to each other, and the color tone of the composition changes to visually volatilize. It is possible to extremely accurately recognize the remaining efficacy of the sexual drug and its end point. This color reaction is completely non-aqueous and sharp, and is not affected by moisture in the air.

Further, by impregnating, coating or holding a chromogenic drug composition containing the above four components as essential components on a support such as a pulp board, the use is simplified and the mechanism of action is not always clear. However, it shows a stable color tone, and the stability of the drug and the electron-donating color-forming organic compound is increased with time.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, various aspects of the present invention will be described in detail. The non-aqueous volatile agents used in the present invention are those that evaporate under normal use conditions (normal temperature and normal pressure or under heating) and include pyrethroids such as d-arlesrin, empentrin, framethrin, etoproxifene, and resmethrin. Insecticide, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, diethyl fumarate,
Insect repellents and repellents such as N, N-diethyl-m-toluamide;
Insect repellents such as ethyl benzoate, safrole, isosaflor, eugenol, citronellol, anethole, l-carvone, citral, citronellal, nerol, geraniol, linalyl acetate, acetophenone, terpineol, menthone, benzyl benzoate, ethyl phenyl acetate, acetic acid Flavors such as isoamyl and eucalyptol; and insect and fungicide such as cinnamaldehyde and benzaldehyde. The above-mentioned drug is a compound having various effects such as insecticidal, insect repellent, repellent, attracting, aroma, deodorant, antibacterial, antifungal, sterilizing, etc. Various compounds that volatilize and exert their effects can be used, as pesticide compositions, insect repellent compositions, fragrance deodorant compositions, etc. according to their respective medicinal effects, and at room temperature volatilizing drugs according to their volatilization characteristics, heating It can be used for various uses as a fumigant or the like. In addition, each drug may be used alone, or two or more drugs may be used in combination.

Further, the volatile chemicals described above are exemplified, and are not limited to these compounds. Some of these compounds do not exhibit desensitization. In this case, if a solvent having desensitization and having substantially the same volatility as the drug is used, color development according to the residual state of the drug is performed. Is obtained. Conversely, the object of the present invention can be achieved by using a solvent which does not exhibit desensitization and has substantially the same volatility as the drug, if the volatile agent exhibits desensitization. That is, any one of the volatile agent and the volatile solvent may have desensitization. Of course, both the volatile agent and the volatile solvent may have desensitization.

The reason for using a solvent is as follows in addition to the above. It is preferable that the volatile agent can be uniformly dissolved or melted with the electron-donating color-forming organic compound and the developer, but in the case of insoluble or hardly soluble, when forming into a formulation by impregnation or impregnation, of course, , A solvent is required.
Even if the drug has the ability to dissolve these compounds, the drug is highly effective, the compounding amount thereof is small, and even if the amount is insufficient to dissolve the compound, a solvent is required.

The solvent may or may not have a desensitizing property, and can uniformly dissolve the above-mentioned chemicals, the electron-donating color-forming organic compound and the developer, and can stably maintain the dissolved substance with time. Any examples are possible, and examples thereof include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, esters, ethers, ketones, and amides.

If the rate of volatilization of the drug and the rate of volatilization of the solvent are significantly different, adverse effects such as difficulty in accurate indication of the medicinal effect will occur. Therefore, a substance having the same rate of volatilization of the drug and the rate of volatilization of the solvent is used. The solvent may or may not have its own medicinal properties.

Examples of the non-aqueous color-forming organic compound having an electron donating property used in the present invention include triphenylmethanephthalides, fluorans, phenothiazines, indolylphthalides, spiropyrans and the like. Then, as triphenylmethanephthalides, * crystal violet lactone (abbreviation CVL)
* Malachite Green Lactone (abbreviated as MGL, Hodogaya Chemical Industry Co., Ltd.) Fluoranes include: * 1,2-benz-6-diethylaminofluoran
(Trade name: NC-R-1 manufactured by Hodogaya Chemical Industry Co., Ltd.) * 2-bromo-3-methyl-6-dibutylaminofluoran (trade name: NC-R-2 Hodogaya Chemical Industry Co., Ltd.)
* 2- (2-chloroanilino) -6-dibutylaminofluoran (trade name: NC-Black-1 manufactured by Hodogaya Chemical Industry Co., Ltd.) * 3-Diethylamino-6,8-dimethylfluoran
(Product name: NC-O-1 manufactured by Hodogaya Chemical Industry Co., Ltd.) As phenothiazines, * benzoylleucomethylene blue (abbreviation BLMB)
(Made by Hodogaya Chemical Industry Co., Ltd.) * Methoxybenzoyl leucomethylene blue Indolylphthalides include * 3- (1,2-dimethylindol-3-yl) -3
-(4-Diethylamino-2-methylphenyl) -phthalide (trade name: NC-Blue-3 manufactured by Hodogaya Chemical Industry Co., Ltd.) * 3- (1,2-dimethylindol-3-yl) -3
-(4-Diethylamino-2-ethoxyphenyl) -phthalide (Japanese Patent Publication No. 48-21329, filed by Hodogaya Chemical Co., Ltd.) Spiropyrans include * 1,3,3-trimethylindolino-2,2'- Spiro-6'-nitro-8'-methoxybenzopyran * 1,3,3-trimethylindolino-7'-chloro-
β-naphthospiropyran and the like, but these are merely exemplary compounds, and non-aqueous, electron-donating, color-forming organic compounds suitable for the purpose of the present invention are exemplified by the compounds exemplified above. Not limited.

The non-aqueous color-forming organic compound having an electron-donating property suitable for the purpose of the present invention must be (1) colorless or light-colored, stable in air, (2) (3) dissolving in a non-aqueous solvent (oil-soluble), (4) the color fastness to sunlight is high and stable, 5) remains without volatilizing in the state of use of the drug composition,
That is, it is non-volatile or non-volatile,
(6) It is desirable to be able to obtain it industrially at low cost.

Among the above-mentioned color-forming compounds, CVL is satisfactory in terms of color development speed, hue or stability, but is inferior in fastness to sunlight, while BLMB is very slow in color development, but direct color. Even in sunlight, it does not fade at all, and it can be mixed with CVL to interpolate each other's disadvantages and exhibit only the advantages. As in this example, the non-aqueous, color-providing organic compound having an electron donating property suitable for the purpose of the present invention includes not only a single use but also a mixture of two or more.

The above-mentioned electron-donating color-forming organic compound is colorless or pale in color alone, but develops a color in the presence of a developer. Illustrative of the developer used in the present invention is 2,2-bis (4'-hydroxyphenyl).
Propane, dimyristyl 3,3'-thiodipropionate, 2,2'-methylenebis (4-chlorophenol), 4,4'-methylenebis-2,6-di-t-butylphenol, 2,4,6- Tris (3 ', 5'-di-
t-butyl-4'-hydroxybenzyl) mesitylene,
4,4'-thiodiphenol, 4,4'-bis (4-hydroxyphenyl) sulfone, butylidenebis-6-t
-Butyl-m-cresol, p-phenylphenol,
1,1,3-tris (2-methyl-4-hydroxy-5
-T-butylphenyl) butane, 3,5-di-t-butylcatechol, catechol, pt-butylcatechol, methyl gallate, phenyl salicylate, salicylanilide, p-octylphenyl salicylate, pt-butylphenyl salicylate , 2-hydroxy-4-methoxybenzophenone, 2,2 ', 4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4 ,
4'-dimethoxybenzophenone, 2,4-dihydroxybenzophenone, 2-hydroxy-4-n-octoxybenzophenone, β-naphthol, p-cresol,
Hydroquinone, butylhydroxyanisole, 6-t
-Butyl-2,4-xylenol, p-hydroxybenzyl alcohol, 0-tert-butylphenol, t-butylhydroquinone, 2-tert-butyl-6-methylphenol, 2,5-di-tert-butylhydroquinone, p -Propyl-hydroxybenzoate, 1,2,4-trihydroxybenzene, 1,2,3-benzotriazole, etc., and known non-volatile or non-volatile volatile developer in the above-mentioned meaning. Can be used. The developers may be used alone or in combination of two or more. Among these developers, there are many compounds that are also useful as antioxidants and ultraviolet absorbers when mixed with drugs, and the use of a developer having such an effect is effective in stabilizing drugs. Becomes

In the present invention, the mixing ratio of the volatile desensitizing agent or the volatile desensitizing solvent to the electron-donating color-forming organic compound and the developer is usually in a weight ratio of the drug: the electron-donating color-forming organic compound. : Developer = 100: 0.1-50: 0.01
About 100 is sufficient. The more the compounding amount of the electron-donating color-forming organic compound is increased, the higher the coloring density becomes. However, if the compounding amount is too large, uniform mixing and dissolution become difficult, and the volatilization of the drug is suppressed, and the electron-donating color-forming organic compound is increased. It is not preferable because it causes problems such as contamination due to the above. On the other hand, the compounding amount of the color developer is preferably as large as possible in the case of the color-forming drug composition of the present invention, particularly in the case of the holder impregnated with the composition, since the color-forming density is low as a whole. It is not preferable because it causes problems such as difficulty in dissolving and unstable color development. Therefore, the preferred range of the above mixing ratio is 1
00: 0.2 to 30: 0.1 to 50.

The color-forming drug composition of the present invention is, as described in the item of "action", a non-aqueous volatile desensitizing drug and / or a non-aqueous volatile desensitizing solvent. This suppresses the coloration of the color-forming organic compound having an electron donating property with a non-aqueous and electron-accepting color developing agent, and generates color by the volatilization of the above-mentioned chemical and / or solvent. Therefore, whether or not the electron-donating color-forming organic compound forms a color depends on the degree of the reactivity (desensitization) of the desensitizing agent and / or the desensitizing solvent and the reactivity of the developer (color developing property). Decided. While the above-mentioned drug and / or solvent remains, the coloration of the electron-donating color-forming organic compound needs to be suppressed. Therefore, when the desensitizing properties of the above-mentioned chemicals and / or solvents themselves are weak, a developer having a weak effect is used. As the solvent, those having some medicinal effects can be used. However, if the volatilization rates of the volatile agent and the volatile solvent are significantly different, it becomes difficult to accurately display the medicinal effect. Therefore, those having substantially the same vaporization rate are used.

Examples of such volatile solvents include acetone, methyl ethyl ketone, diethylene glycol dimethyl ether, methyl acetate, ethyl acetate, n-butyl acetate, isoamyl acetate, n-octyl acetate, dimethyl fumarate, methyl n-caproate and n-methyl caproate. Methyl caprate,
Methyl laurate, dioctyl adipate, n-propyl salicylate, ethyl myristate, n-capric acid n
-Amyl, isobutyl undecanoate, isobutyl laurate, ethyl laurate, isoamyl n-caproate,
Dibutyl adipate, butyl carbitol, n-decane, 1,1,1-trichloroethane, coconut oil, triethylamine, diethylamine, acetonitrile, 1,4-
Examples thereof include ketones such as dioxane, n-octyl alcohol, toluene, morpholine, and dimethyl glycol, ethers, esters, alcohols, hydrocarbons, and amines.

The color tone of the electron-donating color-forming organic compound can be red, black, blue, green, violet, orange, yellow, and brown. By appropriately selecting the electron-donating color-forming organic compound, the color developer, and the solvent, the desired color tone, color density, and color change period can be obtained.

When the drug used is not of a type that gradually evaporates and exerts its effect, it can be used for, for example, a drug that does not sublimate or sublimates but gradually decomposes and loses its effect. is there. That is, the former sublimates, and the latter decomposes, whereby the desensitizing property of the drug itself is weakened, and the developer can gradually develop color by increasing the color developing property. In addition, an appropriate volatile solvent having a volatilization rate corresponding to the decomposition rate of the drug may be used, and the color may be adjusted by the volatilization of the solvent. Therefore, the term “volatile” as used in the present invention includes, in addition to a drug that is volatilized without being decomposed in a state of use (at normal temperature and pressure and under heating), a sublimable or degradable drug, and is referred to as “volatile”. Must be interpreted as a broad term that refers to the state in which a drug escapes from a color reaction system.

If necessary, an ultraviolet absorbent, an antioxidant, a desensitizer, a sensitizer, a synergist, a volatilization modifier, and the like can be added to the composition for indicating efficacy of the present invention.

Further, in the present invention, a carrier is used in order to obtain an effective and effective indication of efficacy when using the above-mentioned composition for indicating efficacy. By using the holder,
The liquid volatile drug can be handled as a solid, can suppress contamination, can clarify the color change of the drug composition, and in some cases can further improve the stability over time. .

The holding member may be any holding member that can stably hold the drug composition and can visually determine the color change, such as paper, non-woven fabric, cloth, wood, pulp, inorganic polymer, Inorganic porous materials (silicates, silica, zeolites, etc.), organic polymer materials (cellulose, polyethylene,
Polyvinyl chloride, polypropylene, polyvinyl alcohol, vinyl acetate-vinyl chloride copolymer, styrene-divinylbenzene copolymer, etc.), gelling substances (agar, carrageenan, starch, gelatin, alginic acid, etc.), sublimable substances (adamantane, Cyclododecane, norbornane, trimethylnorbornane, endo-trimethylenenorbornane, paradichlorobenzene, naphthalene, camphor, etc.) and the like, and one or more of these can be used in combination; mat, sheet, film, It can be used in any dosage form such as gel, powder, granule, and tablet.

In manufacturing the drug-effect-indicating drug carrier of the present invention, a method such as drop coating, dip coating, spray coating, printing, brush coating, etc., or sticking to the holder is used. Available. When the mixture is applied to the support by application, impregnation, or the like, the support can be applied, impregnated, or the like, in the form of a dot, one surface, or a pattern, over the entire surface, partially, or on the support.

The concentration of the drug composition in the support may be such that a desired color change can be visually recognized, and it depends on the color of the support itself. (Or saturation holding amount) of about 10 to 80% is appropriate.

However, a carrier that does not penetrate or diffuse the drug composition liquid, such as metal, plastic, or synthetic paper, or a drug composition that does not penetrate or diffuse (solid, fluid, or semi-fluid, etc.), for example, In the case of applying or printing a composition containing an inorganic substance, a polymer substance and the like in a spot manner, the composition need not be in the above range. When an organic polymer compound or a sublimator is used as a support,
The drug composition cannot be held (contained) at a high concentration. In such a case, it is possible to use a method of mixing after adsorbing on an adsorbent having a high holding ability.

The support may contain a binder, an antioxidant, an ultraviolet absorber, a dispersant, a fixing agent, and the like, if necessary. Further, the holder may itself have a color, and in this case, a color change from a color to a color is obtained.

In the use of the drug-indicating drug carrier of the present invention, when it is necessary to prevent contamination due to color shift, if necessary, a gas-permeable nonwoven fabric, paper,
Packaging with cloth, film, or the like, storage in a plastic container, paper container, or the like, or film treatment, lamination processing, or the like can be performed, and a product form can be appropriately selected according to the use.

[0041]

[Examples] First, as a preliminary test, various non-aqueous volatile desensitizing agents, a non-aqueous color-forming organic compound having an electron donating property, and a non-aqueous color developing agent having an electron-accepting property were used. A color reaction was observed. (Examples 1 to 55)

Example 1 N, N-diethyl-m-toluamide 100 parts by weight NC-R-1 ^*) 2 parts by weight Bisphenol A 4 parts by weight *) Fluoran compound, manufactured by Hodogaya Chemical Industry Co., Ltd. A solution prepared by applying 0.5 g of a stock solution blended and prepared in a ratio to a linter mat (2.8 mm thick, 2.2 × 3.5 cm) is hung in a veneer box (with an internal volume of about 900 l), and a repellent (N , N-diethyl-m-toluamide) was examined for the relationship between the color change of the mat accompanying the volatilization of the mat and the residual amount of the drug. Table 1 shows the results.

[0043]

[Table 1]

As apparent from Table 1 above, drugs N, N
-Diethyl-m-toluamide volatilized and hardly remained in the impregnated body, and when the repellent effect began to disappear, the color change of the impregnated body started, and when the repellent effect disappeared, the color change of the entire impregnated body was completed.

Examples 2 to 55 (A) Various chemicals and fragrances having repellent, insect repellent, insecticidal, fungicidal and bactericidal effects, (B) various electron-donating color-forming organic compounds, and (C) various developers In general, (A): (B):
(C) = mixed and dissolved in a weight ratio of 100: 2: 4, 0.5 g in linter mat 2.8 mm thick, 2.2 × 3.5 cm
The coated product was left in a constant temperature bath at 20 to 40 ° C., and the color change of the mat was observed. The results are shown in Tables 2 and 3.
For the drugs having various effects, red, blue, orange, and black color changes were obtained, and the end points could be clearly recognized.

[0046]

[Table 2]

[0047]

[Table 3]

Next, an example in which a solvent was added to the three components of the above preliminary test will be described below. (Examples 56 to 76)

Examples 56 to 76 (A) Agents having various efficacies, (B) various electron-donating color-forming organic compounds, (C) various developers, and (D) solvents were generally used as (A) :( B) ) :( C) :( D) = 100: 2:
The mixture was mixed and dissolved at a weight ratio of 4: 100, and the color change of the mat was observed in the same manner as in Examples 2-55. Table 4 shows the results. As is apparent from Table 4, when the drug (A) itself is a solid, when the above components (B) and (C) cannot be dissolved even in a liquid, or when the color change is unknown even if the drug can be dissolved, The end point of the drug effect can be clearly recognized by adding one or more of suitable solvents (preferably having various effects similarly to the above-mentioned drug (A)). In this case, those having a vapor pressure close to the used drug (A) are preferable, but care must be taken because the color changes slightly and the end point timing changes depending on the solvent used.

[0050]

[Table 4]

Next, the following test was conducted in order to see the action of the color developer. (Examples 77 to 99)

Examples 77 to 99 (A) N, N-diethyl-m-toluamide as a drug,
(B) NC-R- as an electron-donating color-forming organic compound
(A): (B): (C) =
The components were mixed and dissolved at a weight ratio of 100: 2: 4 to 6, and the color change of the mat was observed in the same manner as in Examples 2-55. Table 5 shows the results. The drug (A) and the electron-donating color-forming organic compound (B) are unified into a certain compound, and the developer (C)
Was varied. As is clear from Table 5, various color changes could be obtained only by changing the developer without changing the electron-donating color-forming organic compound.

[0053]

[Table 5]

Next, the test of the color composition held in the impregnated body is shown below. (Examples 100 to 116)

Examples 100 to 116 (A) Drug N, N-diethyl-m-toluamide, (B)
Electron-donating color-forming organic compound NC-R-1 and (C) developer 2,2'-methylenebis (4-chlorophenol)
(A) :( B) :( C) = 100: 2: 10 in a weight ratio of 100: 2: 10. The color change was observed. Table 6 shows the results.

In Examples 100 to 105, linter mats and filter papers (No.
1), Kent paper, kraft paper, Japanese paper, cardboard (Showa cover)
And the color change was observed in the case where the stock solution was applied to a size of 2.2 × 3.5 cm and applied about 2/3 of the saturation amount. In Examples 106 to 112, cupra cloth, silk cloth, cotton cloth, wool cloth, acrylic cloth, polyester cloth, rayon cloth (all J
5 × 5c each for IS dye fastness test)
The color change was observed for a sample having a size of m and the stock solution applied about 2/3 of the saturated amount. Example 11
3 is a silica plate (Kiesel manufactured by Merck) as an impregnating material.
Using gel 60), color change was observed for those coated with 2/3 of the saturation amount. In Example 114, the color change was observed for 100 parts of powdered polyvinyl alcohol impregnated with 50 parts of the stock solution. In Example 115, 100 parts of linoleum (manufactured by Toyo Linoleum) was added as an impregnating material, and 50 parts of the stock solution was added and mixed. Example 11
In No. 6, 50 parts of the stock solution and 50 parts of diethyl phthalate were added to 100 parts of polyvinyl chloride powder, and the mixture was heated and melted, cooled, and softened into a sheet to observe color change.

[0057]

[Table 6]

Next, the stability of the impregnated body holding the coloring composition over time was tested. (Examples 117 to 141)

Examples 117 to 141 Except that various compounds shown in Table 7 were used, the impregnated body produced in the same manner as in Example 1 was completely sealed with an impermeable packaging material, and then placed in a constant temperature chamber at 40 ° C. It was stored and analyzed every 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months to determine the content (residual rate) of the drug in the packaging material. Also,
The color change of each impregnated body during storage and after opening the packaging material was examined. Each impregnated body was analyzed three times at a time, and three samples were analyzed for color change.
Used. Table 8 shows the analysis results.

[0060]

[Table 7]

[0061]

[Table 8]

Color Change Investigation Results None of the impregnated bodies after one month, two months, three months, six months, twelve months, eighteen months, and twenty-four months had no color change during storage, and had no color change function after opening. There was no deterioration, and the color developed from colorless to colored in accordance with the combination of the electron-donating color-forming compound and the developer, and the color-developing density showed almost no difference irrespective of the elapsed time.

As can be seen from the above results, the prescription according to the present invention can be used stably without decomposing a drug having a medicinal effect with the passage of time or losing the function of discoloration.

In each of the above tables, the abbreviations for the electron-donating color-forming organic compounds indicate the following compounds. NC-R-1: Fluoran compound manufactured by Hodogaya Chemical Industry Co., Ltd. NC-R-2: 〃 NC-Black-1 〃 NC-O-1: 〃 NC-Blue-3: 〃 Indolyl phthalate CVL: crystal violet lactone triphenylmethanephthalide compound BLMB: benzoylleucomethylene blue phenothiazine compound The abbreviations of the fungicides are as follows. α-BCA: α-bromocinnamaldehyde BMC: 6-tert-butyl-m-cresol

[0065]

As described above, the drug efficacy indicating composition according to the present invention comprises a non-aqueous volatile drug, a non-aqueous volatile solvent and a non-aqueous color-forming organic compound having an electron donating property. ,
Four components of non-aqueous and electron-accepting developer are essential components
The non-aqueous volatile agent and the non-aqueous volatile solvent have the same volatility, and both or one of the agent and the solvent are desensitizing , and
The volatile drug and the volatile solvent are volatilized and remain
Is low, the color developing organic compound and the developer
Since the reaction is initiated to generate color, the reaction of the color developer with respect to the electron-donating color-forming organic compound is suppressed while the above-mentioned chemicals and / or solvent remain, and the color is developed. It suppresses color and causes coloration by volatilization of the above-mentioned drug and / or solvent. For this reason, the user can visually and very accurately and sharply recognize the intermediate point and the end point of the medicinal effect by the color change. Further, since this color reaction occurs completely in a non-aqueous system, the action of the indicator is not affected by the humidity in the air unlike the conventional one.

Therefore, in the field where volatile compounds have been used, the problems caused by unclear and inaccurate end points of the drug effect can be solved at once. In addition, the drug-effect-indicating drug carrier according to the present invention is obtained by impregnating, coating, or holding the above-described drug-effect-indicating composition in paper, cloth, pulp, porous substance, polymer substance, gelling substance, and the like. This makes it very easy and inexpensive to manufacture various dosage forms such as mats, gels, powders, and granules, and also allows the handling of liquid volatile chemicals as solids, preventing contamination. In addition to this, a stable color tone can be obtained, the color change can be made clearer, and the stability over time can be improved.

Claims (2)

(57) [Claims] Claims 1. A non-aqueous volatile agent, a non-aqueous volatile solvent, a non-aqueous color-forming organic compound having an electron donating property, and a non-aqueous color developing agent having an electron-accepting property are essential. Ingredients
The non-aqueous volatile agent and the non-aqueous volatile solvent have the same volatility, and both or one of the agent and the solvent are desensitizing , and
The volatile drug and the volatile solvent are volatilized and remain
Is low, the color developing organic compound and the developer
A drug efficacy indicating composition characterized in that a reaction is initiated to produce a color . 2. Four components are essential : a non-aqueous volatile agent, a non-aqueous volatile solvent, a non-aqueous color-forming organic compound having an electron-donating property, and a non-aqueous-type developer having an electron-accepting property. Ingredients
The non-aqueous volatile agent and the non-aqueous volatile solvent have the same volatility, and both or one of the agent and the solvent are desensitizing , and
The volatile drug and the volatile solvent are volatilized and remain
Is low, the color developing organic compound and the developer
A drug-effect-indicating drug carrier obtained by impregnating, applying, or holding a drug-effect-indicating composition in which a reaction is initiated to cause coloration.