JPH09301873A - Solubilization of sulfonamide and aqueous medicine obtained by solubilizing sulfonamide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an aqueous medicine comprising a sulfonamide solubilized in weak acidity to a pH in the vicinity of neutrality. SOLUTION: This aqueous medicine comprises a sulfonamide, a polyvinyl pyrrolidone and a cyclodextrin in which the sulfonamide is solubilized in weak acidity to neutrality, especially at pH3-7.5 in which the sulfonamide is extremely difficult to be dissolved in water. Sulfadiazine, sodium sulfisomidine, etc., in >=1W/V% are used as the solfonamide. A straight-chain polyvinyl pyrrolidone having 10,000-700,000 molecular weight in 0.5-10W/V% concentration is used as the polyvinyl pyrrolidone. A cyclodextrin selected from α, β and γ- cyclodextrins in 1-8W/V% concentration is used as the cyclodextrin. The product of the concentration of the polyvinyl pyrrolidone and that of the cyclodextrin is >=4[W/V%]<2> . The aqueous medicine containing the sulfonamide is useful as an external agent, an eye drop, a nasal drop, an ear drop, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for solubilizing a sulfa drug and an aqueous drug in which the sulfa drug is solubilized.

[0002]

BACKGROUND OF THE INVENTION Sulfa drugs are a group of chemotherapeutic agents having antibacterial activity against some Gram-negative bacteria and Gram-positive bacteria, Chlamydia and certain protozoa, and are used systemically and locally. There is. Compounds classified as sulfa drugs are numerous and include, for example, sulfadiazine, sulfisoxazole, sulfisomidine, sulfadimethoxine, sulfamethoxypyridazine, sulfamethoxazole, sulfaetidol, sulfamethomidine,
Examples thereof include sulfaphenazole, sulfaguanidine, phthalylsulfathiazole, succinylsulfathiazole, and salts thereof.

Sulfa drugs are also used as an aqueous solution in the form of eye drops and the like, but they are very difficult to dissolve in water in the range of weakly acidic to neutral (pH 4.5 to 8) which is preferable as a drug for topical application. Water solubility is improved on the alkaline side. Therefore, the commercially available sulfa drug-containing eye drops have a pH set to 8.2 or higher. However, such high pH compromises the stability of many drugs. From this, it was difficult to mix other drugs in the aqueous liquid preparation containing the sulfa drug in a dissolved form.

Against this background, attempts have been made to solubilize sulfa drugs by adding various solubilizing agents at pHs around weakly acidic to neutral. At present, however, satisfactory results have been obtained. Has not been done.

[0005]

An object of the present invention is to provide an aqueous drug containing a sulfa drug dissolved therein at a pH in the vicinity of weak acidity to neutrality.

[0006]

Means for Solving the Problems The present inventors have produced a synergistic solubilizing action by using a combination of polyvinylpyrrolidone and cyclodextrins, which alone have little solubilizing effect on sulfa drugs, It was found that the sulfa drug can be much more solubilized at a pH around weakly acidic to neutral. That is, the present invention
Provided is a weakly acidic to near neutral aqueous drug containing a sulfa drug, polyvinylpyrrolidone and cyclodextrins.

That is, the present invention is an aqueous drug containing a sulfa drug dissolved therein, wherein the sulfa drug is solubilized by containing polyvinylpyrrolidone and cyclodextrins, and the sulfa drug. Is a method for solubilizing water in water, wherein polyvinyl pyrrolidone and cyclodextrins are contained together with the sulfa drug.

As the cyclodextrins, various substituted and unsubstituted ones can be used. For example,
Any of α, β or γ-cyclodextrin may be used. Whether a cyclodextrin of α, β or γ is optimal for a given sulfa drug can be determined by a person skilled in the art by carrying out a simple solubility test using the sulfa drug according to the method described in the present invention. It can be easily determined at any time. Also, various substituted cyclodextrins may be used. Examples of these are hydroxymethyl-β-
Cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxyisopropyl-β-cyclodextrin, β-cyclodextrin sulfonic acid, and α and γ-cyclodextrin having these substituents. . Of these, α, β and γ-cyclodextrin are particularly preferable.

The sulfa drugs which can be used in the present invention include:
All sulfa drugs used as antibacterial agents are included, and for example, the sulfa drugs specifically listed above are included.

Polyvinylpyrrolidone has a linear molecular weight of 10,000 as described in "Cosmetic Raw Material Standard, Second Edition".
Any polyvinylpyrrolidone of up to 700,000 can equally be used in the present invention in terms of its synergistic solubilizing effect. Of these polyvinylpyrrolidones, those having a molecular weight of 15,000 to 50,000 are more preferable in consideration of the properties of the aqueous drug, the feeling of use and the like.

The concentration of polyvinylpyrrolidone used is
It is effective for solubilizing sulfa drugs in a wide range of 0.5 to 10 W / V%, more preferably 0.5 to 8 W / V%, still more preferably 1 to 8 W / V%, particularly preferably 2 to 8%.
W / V%. The concentration of polyvinylpyrrolidone used need not be higher as long as the given sulfa drug is sufficiently solubilized in relation to the cyclodextrin used in combination. Therefore, depending on the given sulfa drug and the amount thereof, for example, it may be selected in the range of 0.5 to 6 W / V%, 2 to 4 W / V% and the like.

The concentration of cyclodextrins used is
Preferably 1-8 W / V%, more preferably 2-8 W /
V%, still more preferably 4 to 8 W / V%. As stated above for the concentration of polyvinylpyrrolidone,
The concentration of the cyclodextrins used need not be higher as long as the given sulfa drug is sufficiently solubilized in relation to the polyvinylpyrrolidone used in combination. Therefore, depending on the given sulfa drug and its amount, it may be selected in the range of, for example, 1 to 6 W / V%, 2 to 4 W / V%, and the like.

Preferably, the polyvinylpyrrolidone concentration is 0.5 to 10 W / V% and the cyclodextrin concentration is 1
.About.8 W / V%, and the product of the concentration of polyvinylpyrrolidone and the concentration of cyclodextrins is 4 [W / V
%] If the concentrations of polyvinylpyrrolidone and cyclodextrins are selected within the range of ² or more, a particularly excellent solubilizing effect can be obtained.

The method for solubilizing a sulfa drug according to the present invention comprises:
Weakly acidic to neutral, which makes it very difficult to dissolve sulfa drugs in water,
Especially in the range of pH 3.0-7.5, and especially p
It is advantageous in the range of H3.0 to 7.0.

The present invention is also particularly useful in dissolving sulfa drugs in water of such acidity to concentrations of 1.0 W / V% and above.

In the following, as an example, polyvinylpyrrolidone and cyclodextrin alone and polyvinylpyrrolidone were prepared by using sulfisomidine sodium as a sulfa drug, polyvinylpyrrolidone K-30 as a polyvinylpyrrolidone, and β-cyclodextrin as a cyclodextrin. The test results for the effect of the combined use on the solubility [W / V%] of the sulfa drug are shown below.

[Solubilization test] (1) Change in solubility of sulfa drug by polyvinylpyrrolidone alone 2.5 g of sulfisomidine sodium was mixed with water at room temperature, and 0.5, 1.0, 2.0, 4.0 or 8.0 W / V% was added thereto. Polyvinylpyrrolidone K-25 (Japanese Pharmacopoeia, average molecular weight 25,000; hereinafter referred to as "PVP") was added thereto so as to stir, and the pH was adjusted to 6.0 with hydrochloric acid, and the volume was adjusted to 100 mL. Observe the appearance of these aqueous agents, then 0.45μ
The mixture was filtered through a m filter and the concentration of sulfisomidine in the filtrate was measured by HPLC.

The measurement conditions are as follows. (A) Detector: UV spectrophotometer (measurement wavelength 254 n
m) (b) column: YMC-A-302 (c) column temperature: 40 ° C. (d) mobile phase: 0.05M potassium dihydrogen phosphate: methanol = 75: 25 (e) flow rate: 0.6 mL / min

For each concentration of PVP [W / V%] in Table 1, (1) appearance of the aqueous drug, (2) amount of sulfisomidine dissolved in the filtrate [W / V%], and (3) ) PVP
Increase in the amount of sulfisomidine dissolved [W /
V%] (that is, the amount of dissolution when PVP is added-P
The amount of dissolution when VP is not added) is shown.

[0020]

[Table 1]

As shown in the table, all the aqueous agents had a cloudy appearance and could not sufficiently dissolve 2.5 W / V% sulfisomidine. From the data of the dissolution amount, although the dissolution amount of sulfisomidine increased with the increase of the concentration of PVP, the increase was not sufficient,
It has been found that the addition of P to concentrations of 2.0, 4.0 and 8.0 W / V% can dissolve only 0.5, 0.6 and 1.0 W / V% sulfisomidine, respectively. At least some margin is required for solubilization in the production of an actual aqueous drug, so the concentration of sulfisomidine that can be produced by using PVP alone at 8.0 W / V% is 1 W / V%.
Clearly, less than. Even if PVP is not added (zero W / V%), sulfisomidine is 0.2
It is dissolved at a concentration of W / V%, and the addition of PVP at the above concentrations is 0.2, 0.2, 0.3, 0.4 and 0.8 W / V, respectively.
It only increased the amount of sulfisomidine dissolved by%.

(2) Change in solubility of sulfa drug by β-cyclodextrin alone 2.5 g of sulfisomidine sodium was mixed with water at room temperature so that 0.5, 1.0, 2.0, 4.0 or 8.0 W / V% was obtained. β-Cyclodextrin (hereinafter “β-CD”) was added and stirred, and the pH was adjusted to 6.0 with hydrochloric acid, and the volume was adjusted to 100 mL. The appearance of these aqueous agents was observed, then filtered through a 0.45 μm filter, and the concentration of sulfisomidine in the filtrate was measured by HPLC. The measurement conditions are as described in (1) above.

Table 2 below shows each concentration of β-CD [W / V%].
(1) Appearance of aqueous drug, (2) Amount of sulfisomidine dissolved in the filtrate [W / V%], and (3)
The increase [W / V%] of the amount of sulfisomidine dissolved by the addition of β-CD at each concentration (that is, the amount of dissolution when β-CD was added-the amount of dissolution when β-CD was not added) is shown.

[0024]

[Table 2]

As shown in the table, all of the aqueous drugs had a cloudy appearance and could not sufficiently dissolve 2.5 W / V% sulfisomidine. From the data of the amount of dissolution, although the amount of sulfisomidine dissolved increased with the increase of the concentration of β-CD, the increase was not sufficient,
When both CD and CD were added at concentrations of 4.0 and 8.0 W / V%, only 0.6 W / V% of sulfisomidine was dissolved, and the increase in the amount of sulfisomidine dissolved was 4.0% of β-CD.
It was found that the plateau was almost reached in%. Since at least some leeway is required for solubilization in the actual production of an aqueous liquid agent, β-CD alone gives 8.0 W / V.
%, The concentration of sulfisomidine that can be produced is 0.6
It is clear that it is less than W / V%. In addition, β-C
Even when D is not added (zero W / V%), sulfisomidine is dissolved at a concentration of 0.2 W / V%, so the addition of β-CD at each of the above concentrations was 0.1, 0.1 and 0.2, respectively.
, 4.0 and 0.4 W / V% only increased the amount of sulfisomidine dissolved.

As described in (1) and (2) above, 8.0 W / V
Each of PVP and β-CD at a concentration of up to 10% alone can dissolve sodium sulfisomidine at a pH of 6.0 at room temperature up to a concentration of 1.0 and 0.6 W / V%, respectively. In addition, PVP and β-CD at a concentration of up to 8.0 W / V% each dissolved sulfisomidine at a maximum of 0.8 when compared to the case of no addition.
And only 0.4 W / V%. From this result, even if PVP and β-CD were used together at the highest concentration of 8 W / V%, the increase in the amount of dissolution due to each was 0.8 W and the sum of 1.2 W / V% was 1.2 W / V%.
However, it was predicted that the effect of solubilization would not be exerted, and that sulfomimidine could be dissolved at a maximum of 1.4 W / V% together with the dissolution amount of 0.2 W / V% in the case where the solubilizing agent was not added.

(3) Change in solubility of sulfa drug by combined use of polyvinylpyrrolidone and β-cyclodextrin 2.5 g of sodium sulfisomidine was mixed with water at room temperature so that the concentration was 2.0 or 4.0 W / V%. PVP
And .beta.-CD at 0.5, 1.0, 2.0, 4.0 or 8.0 W / V% and stirred, and pH 6.0 with hydrochloric acid.
After adjusting to, the volume was raised to 100 mL. Observe the appearance of these aqueous agents and then filter through a 0.45 μm filter to determine the concentration of sulfisomidine in the filtrate by HPLC.
Was measured by The measurement conditions are as described in (1) above.

Tables 3 and 4 below show 2.0 and 4.0, respectively.
Β-C at each concentration in the case of PVP at a concentration of W / V%
Sulfisomidine aqueous drug containing D, (1)
Its appearance, (2) amount of sulfisomidine dissolved in the filtrate [W / V%], and (3) shown in Tables 1 and 2.
Solubilizing effect of PVP alone at 2.0 and 4.0 W / V% (0.3 and 0.4 W / V%, respectively) and 0.5, 1.0, 2.0
, 4.0 and 8.0 W / V% concentration of β-CD alone (0.1, 0.1, 0.2, 0.4, 0.4 W respectively)
/ V%), the predicted dissolution amount of sulfisomidine [W / V%] calculated by the formula "predicted dissolution amount = 0.2 + solubilizing effect with PVP alone + solubilizing effect with β-CD alone".
Is shown.

[0029]

[Table 3]

[0030]

[Table 4]

As shown in Tables 3 and 4, PV
When P was contained at concentrations of 2.0 and 4.0 W / V%, the solubility of sulfisomidine was predicted to increase from the effect of polyvinylpyrrolidone and β-cyclodextrin alone as the concentration of β-CD increased. It increased rapidly compared to the “amount”, and increased by more than 2.5 times compared to the predicted amount. Dissolved amount of sulfisomidine at β-CD concentration of 8.0 W / V% in Table 3 is 2.5 W / V%, and dissolved amount of sulfisomidine at β-CD concentration of 4.0 and 8.0 W / V% in Table 4 is 2.5 W / V%. Indicates that the total amount of sulfisomidine present in the solution was dissolved, and therefore the concentration capable of dissolution is judged to be higher than 2.5 W / V%. From these results shown in Tables 3 and 4, P
It is clear that the combination of VP and β-CD acts synergistically rather than additively on the solubilization of sulfisomidine.

Based on the results of Tables 1 to 4, β-CD and PV
Solubility of sulfisomidine with respect to the concentration of P [W / V
%] Is shown in a three-dimensional graph in FIG. The horizontal axis in the graph is β
-CD concentration [W / V%], the front and rear axes are PVP concentration [W / V
V%], the height represents the solubility of sulfisomidine [W / V%], and the numerical value in parentheses () is the amount of sulfisomidine dissolved [W / V%].
/ V%]. In drawing, CD in Table 3 is 0
% Sulfisomidine dissolution rate 0.7 W / V% and Table 1 PVP 2 W / V% Sulfisomidine dissolution rate 0.5 W / V%
It was determined that the difference from V% was due to measurement error, and the average value of 0.6 W / V% was plotted. Similarly, in Table 4, the dissolution amount of sulfisomidine when β-CD is 0% is 0.8.
The difference between the W / V% and the amount of sulfisomidine dissolved in PVP4 W / V% in Table 1 of 0.6 W / V% was also judged to be due to a measurement error, and the average value thereof, 0.7 W / V%, was plotted. In FIG. 1, points based on measured values are indicated by “●”, the measured points are connected by a straight line parallel to a vertical plane including the β-CD axis or the PVP axis, and β-C is drawn on these straight lines.
Points at which the D coordinate or the PVP coordinate was an integer of 0 to 8 [W / V%] were further plotted, and the points were connected by a straight line similarly to the actual measurement point. In Tables 3 and 4, the dissolved amount is 2.
At the point of 5 W / V%, the solubility is higher than that value but cannot be specified. Therefore, assuming continuity with other parts of the graph, a dashed line is arbitrarily extrapolated above the measured value.

Referring to FIG. 1, the solubility of sulfisomidine rapidly increased depending on the concentrations of both β-CD and PVP, and the combination of β-CD and PVP showed that the solubility of sulfisomidine was increased in Table 1. And it can be clearly seen from Table 2 that a synergistic effect is obtained rather than the mere additive effect that can be expected. In the graph, the remarkable increase in solubility is, for example, 1 W / V% of PVP.
Is clearly observed at 4 W / V% β-CD (point A “◯”, solubility 1.3: read from the graph). Also, at 2 W / V% of PVP, β- of 2 W / V /%
A significant increase in solubility was obtained with CD (point B, solubility 1.
2) and β-C even at 0.5 W / V% of PVP
A remarkable increase in solubility is clearly observed when combined with 8 W / V% of D (point C "○", solubility 1.3).
: Read from the graph). Furthermore, PVP 4W / V%
In the case of 1 W / V% β-CD, a marked increase in solubility was obtained (point D, solubility 1.1). 8W of PVP
At / V% and higher concentrations, the exact value is unknown due to lack of measured values, but from the shape of the whole graph, synergistic solubilization is further enhanced by β-CD of 1 W / V%. Obviously, it is.

Comprehensively judging from the above results, PVP
The effect of the combination of β-CD with β-CD is that the concentration of PVP is 0.5 or more (for example, 0.5 to 10 W / V%) and the concentration of β-CD is 1 to 8 W / V%, and The product of the concentration of PVP and the concentration of β-CD is 4 [W / V
%] It can be seen that it is particularly noticeable in the range of ² or more. The above test example is PVP.
Although polyvinylpyrrolidone K-25 was used as the polyvinylpyrrolidone, the difference with other molecular weight types of polyvinylpyrrolidone was not observed in terms of the effect of synergistic solubilization in combination with CD.

[0035]

BEST MODE FOR CARRYING OUT THE INVENTION The respective concentrations of polyvinylpyrrolidone and cyclodextrins used in the solubilization of the sulfa drug according to the present invention can be increased or decreased depending on the amount of the sulfa drug to be solubilized. Generally, the limit amount of polyvinylpyrrolidone (or of cyclodextrin) capable of solubilizing a specific amount of sulfa drug varies in inverse proportion to the amount of cyclodextrin (or of polyvinylpyrrolidone). Therefore, in the production of the aqueous drug according to the present invention, the respective concentrations of PVP and cyclodextrins may be appropriately determined within a range sufficient for solubilizing a given sulfa drug.

The solubilization according to the present invention can be applied to various sulfa drugs. Examples of such sulfa drugs are sulfadiazine, sulfisoxazole, sulfisomidine, sulfadimethoxine, sulfamethoxypyridazine, sulfamethoxazole, sulfaetidol, sulfamethomidine, sulfaphenazole, sulfaguanidine. , Phthalylsulfathiazole, succinylsulfathiazole and salts thereof.

The cyclodextrins used in the present invention may be any of α, β or γ-cyclodextrin. Whether a cyclodextrin of α, β or γ is optimal for a given sulfa drug can be determined by a person skilled in the art by carrying out a simple solubility test using the sulfa drug according to the method described in the present invention. It can be easily determined at any time. Also, various substituted cyclodextrins may be used. Examples thereof are hydroxymethyl-β-cyclodextrin, hydroxyethyl-β-
Examples include cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxyisopropyl-β-cyclodextrin, β-cyclodextrin sulfonic acid, and α- and γ-cyclodextrin having these substituents.

The present invention has a range from near neutral to weakly acidic, for example, pH 3.
In -7, it can be widely used for the preparation of various aqueous drugs containing sulfa drug in dissolved form. Examples of such agents include, but are not limited to, external preparations, eye drops, nasal drops, ear drops and the like.

The sulfa drug-containing aqueous drug according to the present invention contains other medicinal components, buffers, as long as it is pharmaceutically acceptable,
It may contain an isotonicity agent, a preservative and the like. Examples of other medicinal components include vitamins (pyridoxine hydrochloride, cyanocobalamin, flavin adenine dinucleotide, etc.), vasoconstrictors (nafazoline hydrochloride, etc.), antihistamines (chlorpheniramine maleate, diphenhydramine hydrochloride, etc.), local anesthetics (hydrochloric acid, etc.). Dibucaine) and anti-inflammatory enzymes (lysozyme chloride, etc.). As the buffering agent, various buffering agents commonly used for aqueous agents can be used. Examples thereof include sodium hydrogen phosphate, sodium dihydrogen phosphate, boric acid, borax, sodium citrate, sodium glutamate, sodium aspartate and the like. Examples of the osmotic pressure adjusting agent include salts such as sodium chloride, polyols such as glycerin, mannitol and sorbitol. Examples of the preservative include benzalkonium chloride, parabens, chlorobutanol, chlorhexidine gluconate and the like.

[0040]

EXAMPLES The following are typical examples of the present invention applied to the form of eye drops. In the examples, "PVP (K-3
0) ”is the average molecular weight of the 12th revised Japanese Pharmacopoeia 40,00
It is a polyvinylpyrrolidone of 0. [Example 1] Eye drops The following components were mixed by a conventional method to give a clear solution, which was sterilized by filtration to obtain eye drops. Sulfisomidine sodium 2.5 g β-CD 7.0 g PVP (K-30) 3.0 g Pyridoxine hydrochloride 0.1 g Allantoin 0.1 g FAD sodium 0.05 g Hydrochloric acid Suitable amount (pH 6.0) Sterilized purified water Total volume 100 mL * FAD = flavin adenine di nucleotide

Example 2 Eye Drops The following components were mixed by a conventional method to give a clear solution, which was sterilized by filtration to give eye drops. Sulfisomidine sodium 2.5 g Hydroxypropyl β-CD 4.0 g PVP (K-30) 3.0 g Neostigmine methylsulfate 0.005 g Aminoethylsulfonic acid 1.0 g Hydrochloric acid Suitable amount (pH 6.0) Sterilized purified water Total 100 mL

Example 3 Eye Drops The following components were mixed by a conventional method to give a clear solution, which was sterilized by filtration to give an eye drop. Sulfisomidine sodium 2.5 g Hydroxypropyl β-CD 4.0 g PVP (K-30) 3.0 g Panthenol 0.1 g Cyanocobalamin 0.02 g Hydrochloric acid Suitable amount (pH 6.0) Sterilized purified water Total amount 100 mL

Example 4 Eye Drop The following components were mixed by a conventional method to give a clear solution, which was sterilized by filtration to give an eye drop. Sulfisomidine sodium 2.5 g Hydroxypropyl β-CD 4.0 g PVP (K-30) 3.0 g Neostigmine methylsulfate 0.005 g Aminoethylsulfonic acid 1.0 g Hydrochloric acid Suitable amount (pH 7.0) Sterilized purified water Total amount 100 mL

[Brief description of drawings]

FIG. 1 is a graph showing the increase in the solubility of sulfisomidine by the combined use of β-cyclodextrin and polyvinylpyrrolidone K-30.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 47/32 A61K 47/32 G 47/40 47/40 G

Claims (16)

[Claims] 1. An aqueous drug containing a sulfa drug dissolved therein, wherein the sulfa drug is solubilized by containing polyvinylpyrrolidone and cyclodextrins. 2. The cyclodextrins are α, β and γ
-The aqueous drug according to claim 1, which is selected from the group consisting of cyclodextrins. 3. The sulfa drug is sulfadiazine, sulfisoxazole, sulfisomidine, sulfadimethoxine, sulfamethoxypyridazine, sulfamethoxazole, sulfaethidol, sulfamethomidine,
The aqueous drug according to claim 1 or 2, which is selected from the group consisting of sulfaphenazole, sulfaguanidine, phthalylsulfathiazole, succinylsulfathiazole and salts thereof. 4. The polyvinylpyrrolidone has a molecular weight of 10,000.
The aqueous liquid preparation according to claim 1, which is a linear polyvinylpyrrolidone of about 700,000. 5. The concentration of polyvinylpyrrolidone is 0.5 to 10 W.
/ V% and the cyclodextrin concentration is 1 to 8
The aqueous drug according to any one of claims 1 to 4, which is W / V%. 6. The aqueous drug according to claim 5, wherein the product of the concentration of polyvinylpyrrolidone and the concentration of cyclodextrins is 4 [W / V%] ² or more. 7. The method according to claim 1, wherein the pH is 3.0 to 7.5.
Any of the aqueous drugs. 8. The aqueous drug according to claim 1, wherein the concentration of the sulfa drug is higher than 1 W / V%. 9. A method for solubilizing a sulfa drug in water, which comprises incorporating polyvinylpyrrolidone and cyclodextrins together with the sulfa drug. 10. The method of claim 9, wherein the cyclodextrins are selected from the group consisting of α, β and γ-cyclodextrins. 11. The sulfa drug is sulfadiazine, sulfisoxazole, sulfisomidine, sulfadimethoxine, sulfamethoxypyridazine, sulfamethoxazole, sulfaetidol, sulfamethomidine, sulfaphenazole, sulfaguanidine. The method according to claim 9 or 10, which is selected from the group consisting of phthalylsulfathiazole, succinylsulfathiazole, and salts thereof. 12. The polyvinylpyrrolidone has a molecular weight of 10,0.
The method according to any one of claims 9 to 11, which is a linear polyvinylpyrrolidone of 00 to 700,000. 13. The concentration of polyvinylpyrrolidone is 0.5 to 10.
W / V% and the concentration of cyclodextrins is 1 to
The method according to claim 9, which is 8 W / V%. 14. The method according to claim 9, wherein the product of the concentration of polyvinylpyrrolidone and the concentration of cyclodextrins is 4 [W / V%] ² or more. 15. The method according to claim 9, wherein the pH is 3.0 to 7.5. 16. The method according to claim 9, wherein the concentration of the sulfa drug is higher than 1 W / V%.