JPH11246513A - Aqueous liquid agent of azulene - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an aqueous liquid agent of azulene containing an azulene sulfonic acid salt at a high concentration to improve the handiness of preparation, reduce the production cost and enable easy administration and having guaranteed stability as a product. SOLUTION: This aqueous liquid agent of azulene contains an azulene sulfonic acid salt having antiinflammatory activity as an active component. A nonionic surfactant and an alcohol are used in combination at prescribed amounts or more as an agent for improving the water-solubility and stability of the azulene sulfonic acid salt.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an aqueous solution of azulene containing an azulene sulfonate as a medicinal ingredient.
More specifically, the present invention relates to a stable aqueous azulene solution which can be conveniently and hygienically provided as an anti-inflammatory drug for the throat, oral cavity, digestive organs and other areas in dosage forms corresponding to each application.

[0002]

2. Description of the Related Art Azulene derivatives include kama azulene (1,4-dimethyl-7-ethylazulene), which is an essential oil component of chamomile, a plant belonging to the family Chrysanthemum, and guaizulene (1,4-dimethyl), which is an oil component of eucalyptus tree and eucalyptus. -7-isopropylazulene) and the like have long been known as plant-derived antiinflammatory drugs. In particular, an azulene sulfonic acid salt obtained by introducing a sulfonic acid group into guaiazulene is soluble in water, and thus is used for aqueous preparations (aqueous liquid preparations) or preparations in the form of an aqueous solution at the time of use.

[0003] Azulene derivatives have anti-inflammatory action, anti-allergic action, anti-ulcer action, tissue repair accelerating action and the like, and are used in various administration forms for various diseases as highly safe pharmaceuticals. At present, preparations using these azulene derivatives as active ingredients (medicinal ingredients) are used in the fields of internal medicine, ophthalmology, throat, oral cavity, dentistry and dermatology to treat gastritis and gastric ulcer, and treat and prevent inflammatory diseases of mucosal tissues. Widely used for the purpose. Also in the form of liquids, granules, tablets,
There are a wide variety of creams, lotions and toothpastes.

[0004] Azulene sulfonate, one of the azulene derivatives, is water-soluble, but is formulated as a liquid only in some of eye drops and agents for the throat and mouth. Generally,
As solid preparations such as granules, powders, tablets, and troches, they are designed to be dissolved in water at the time of ingestion and used as a dissolution type at the time of use, or designed to be dissolved at the time of administration. This is because the stability of the azulene sulfonate is insufficient,
It is susceptible to decomposition by light, heat, oxygen, etc., causing a decrease in the content and fading of the color peculiar to the azulene sulfonate. Particularly in the case of an aqueous solution of sodium azulene sulfonate, it is more susceptible and has sufficient stability. Because it cannot be secured.

[0005] Various preparations have been made to improve the stability of the azulene sulfonate salt and the like, and addition of antioxidants and sequestering agents (chelating agents such as EDTA), selection of container materials,
Techniques such as gas replacement have been conventionally performed. However, these methods have problems such as restrictions on medication, limitations on the obtained stabilizing effect, and economic costs associated with formulation.

Therefore, various methods for stabilizing an aqueous solution of azulene containing an azulene sulfonate have been proposed as follows.

A method of adding a quaternary ammonium salt such as a tetramethylammonium salt (JP-A-51-125713) and a method of adding a condensed phosphate (JP-A-58-1)
44365) and a method of blending a cationic surfactant or chlorhexidine with a nonionic surfactant (JP-A-59-196816).

However, it is considered that it is difficult for these stabilization methods to maintain long-term stability, and the following various methods have been proposed as methods aiming at more stable preparations.

A method of blending bicarbonate with 30 wt% or more of alcohols (Japanese Patent Publication No. 7-35342), a method of blending an imidazoline-type or glycine-type amphoteric surfactant (Japanese Patent No. 2505513), and A method of adding a polyhydric alcohol at 20 w / v% or more
No. 71) has been proposed.

However, the concentration of the azulene sulfonate to be stabilized is generally studied in the range of 0.01 to 0.05 wt%, centering on the concentration of the aqueous solution used. In another example, it is considered that the blending ratio of an azulene compound containing an azulene sulfonate is preferably 0.1 to 0.5 wt% (Japanese Patent Publication No. 7-35342, Japanese Patent Publication No. 8-32626). That is, the above-mentioned exemplary concentrations are based on the fact that, in the case of sodium azulene sulfonate, which is an azulene sulfonate, an aqueous solution of about 1 w / v% is the upper limit that can be prepared by conventional known techniques.

[0011]

The sodium azulene sulfonate preparation, which is one of the azulene sulfonates, is a solid preparation mainly in order to ensure stability under the restriction of the dosage form.

The use of a liquid preparation facilitates sterilization and homogenization of the preparation, and is suitable for convenience in dosage form.

[0013] However, problems of the aqueous solution of sodium azulene sulfonate include the limitation of the set concentration due to the limitation of the stability and solubility of the preparation. For the stabilization, various techniques described above are disclosed. Regarding the solubility of sodium azulene sulfonate, it is slightly soluble in water,
Poorly soluble in ethanol (Japanese Pharmacopoeia Standard 19)
1997), which is the upper limit at which a 1 w / v% aqueous solution can be prepared as described above. That is, in the azulene high concentration aqueous solution, precipitation of crystals is observed under low temperature storage.

In view of the above, the present invention contains azulene sulfonate at a high concentration in order to further improve the product, such as convenience of preparation, reduction of production cost, and simplicity of administration, and It is another object of the present invention to provide an azulene aqueous solution which can guarantee the stability as a product.

[0015]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, they have been used in various preparations and are known to be highly safe. By combining the activator and alcohol, it is possible to formulate an aqueous solution of azulene containing a high concentration of azulene sulfonate, which was not possible with the conventional technology, and from the conventional stabilization method technology The present inventors have also found that the present invention provides excellent stability and have completed the present invention having the following constitution.

An aqueous solution of azulene containing an azulene sulphonate as a medicinal component, wherein a nonionic surfactant and an alcohol are combined and formulated as an agent for improving the water solubility and stability of the azulene sulphonate. It is characterized by being.

Here, the nonionic surfactant 0.5 to 3
It is preferable to contain 0 w / v% and 5 to 80 w / v% of alcohols, more preferably, a nonionic surfactant 5.
-15% w / v and 20-80% w / v alcohols.

And, as the nonionic surfactant,
It is desirable to select from the group consisting of polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil and polyoxyethylene alkyl ether, or a combination of two or more.

The alcohols may have 2 to 2 carbon atoms.
It is desirable to select from one or a combination of two or more selected from aliphatic alcohols having 4 and polyhydric alcohols having 3 to 6 carbon atoms.

Further, the content of the azulene sulfonate is preferably 0.5 to 10 w / v%, more preferably 1.5 to 6 w / v%.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION (1) The azulene aqueous solution of the present invention has a prerequisite that it contains an azulene sulfonate as a medicinal ingredient.

Here, as the azulene sulfonate,
Sodium salts, potassium salts, ammonium salts and the like can be mentioned.

Here, the content of the azulene sulfonate is preferably 0.5 to 10 w / v%, more preferably 1.5 to 6 w / v%.

By making the concentration of the azulene sulfonate as high as described above, it is possible to achieve the convenience of the preparation, the reduction of the production cost, the simplicity at the time of administration, and the like.

(2) A characteristic requirement is that a nonionic surfactant and an alcohol are combined and compounded as an azulene sulfonate water solubility / stability improver.

As the nonionic surfactant, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene alkyl ether, and the like are preferably used alone or in combination of two or more. Can be used.

Naturally, the nonionic surfactant is HLB (Hydrophlic-lipophilc-bal) which is itself soluble in water.
ance) is about 8 or more, preferably 10 to 18. Specific examples of each of the above nonionic surfactants can include the following. The numbers in parentheses indicate the moles of ethylene oxide (EO) added. HLB increases with the number of moles added.

Polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate and the like.

Polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene (60) hydrogenated castor oil and the like.

Polyoxyethylene (35) castor oil,
Polyoxyethylene (40) castor oil, etc. Polyoxyethylene (23) lauryl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (15) oleyl ether, etc. The content of these nonionic surfactants in an aqueous solution is as follows: ,
It is 0.5 to 30 w / v%, preferably 5 to 20 w / v%.

(2) The alcohols are selected from one or more of aliphatic monohydric alcohols having 2 to 4 carbon atoms and polyhydric alcohols having 3 to 6 carbon atoms. Specific examples of the alcohols include the following. The number in parentheses after the polyhydric alcohol indicates the alcohol valency.

Ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol and the like. Of these, aliphatic alcohols having excellent solubility in water (miscible with water) and no odor are preferred.

Glycerin (3), propylene glycol (2), xylitol (5), sorbitol (6),
The content of the alcohol in the aqueous solution such as mannitol (6) is 15 to 85 w / v%, preferably 20 to 75 w / v%.

The aqueous solution of azulene of the present invention may contain, if necessary, buffers (phosphates, carbonates, citrates, etc.), preservatives (such as phosphates, carbonates and citrates) as long as the effects of the present invention are not impaired. Paraoxybenzoates, sorbates, dehydroacetates, etc.), chelating agents (sodium edetate,
Condensed phosphates), antioxidants (sodium bisulfite, butylhydroxyanisole, dibutylhydroxytoluene, etc.), thickeners (polyvinyl alcohol, carboxymethylcellulose, etc.), flavoring agents (menthol, aspartame, eucalyptus oil, fennel oil, etc.) , Fragrances and the like, and can be applied as internal preparations and external preparations. These additives are used in usual pharmacology, and can be blended as needed within the range normally used.

The aqueous liquid preparation of the present invention can be prepared according to a method generally used for preparation of a liquid preparation, and is prepared generally as follows.

The azulene sulfonate is dissolved in an appropriate amount of purified water in which a nonionic surfactant and alcohol are dissolved, and then, if necessary, a preservative, a stabilizing agent, a pH adjuster, a flavoring agent and the like are added. Add and dissolve completely to prepare.

[0037]

Next, the present invention will be described in more detail with reference to Test Examples, Comparative Examples and Examples, but the present invention is not limited thereto.

<Test Example A> As a test example, a solution was prepared using purified water as a solvent based on the formulations shown in Tables 1 to 3, and sodium azulene sulfonate (azulene SO ₃ Na) exceeding the normal solubility was prepared. The possibility of preparing a high concentration solution of aqueous solution was studied.

Further, the prepared liquid was passed through a membrane filter and filled in a glass container. This was stored at room temperature (about 20 to 30 ° C.) and refrigerator (about 4 to 6 ° C.) temperature conditions, and the stability of the prepared solution was examined.

As an evaluation method in this case, the properties and appearance of the liquid were visually observed, and the results were displayed as follows.

(Result Display) (Evaluation Criteria) ○ Neither the color tone nor the appearance of the liquid is observed. △ The color tone of the liquid is changed, or a small amount of suspended matter or sediment is observed. Χ A large amount of suspended matter or sediment is observed. Yes-Not performed The test results are as shown in Tables 1-3.

Ethanol and glycerin, which are representative examples of cationic or anionic surfactants and alcohols, did not have the effect of increasing the solubility of the azulene SO ₃ Na aqueous solution (Table 1. Test Nos. 6).

In a solution to which various nonionic surfactants are added, the solubility of azulene SO ₃ Na is enhanced, and it is possible to prepare an aqueous solution of azulene SO ₃ Na of 1 w / v% or more which cannot be usually prepared. (Table 1. Test Nos. 7 to 7)
16).

In this case, although it differs depending on the type of the nonionic surfactant, the nonionic surfactant having an amount of about 1.5 to less than 2 times the amount of azulene SO ₃ Na can be prepared with a high-concentration aqueous solution of azulene. Proved difficult (Test No. 7
・ See 12.15). However, these aqueous solutions are unstable when the blending ratio of the surfactant is about 1.5 to 2 times or when the azulene SO ₃ Na concentration is high,
Precipitates were observed in refrigerator storage and subjected to low-temperature stability (Test Nos. 8, 9, 13, 14, 16).

When various alcohols are added to an aqueous solution containing azulene SO ₃ Na and a nonionic surfactant,
It was confirmed that the dissolution assisting effect was further increased as compared with the case where the nonionic surfactant alone was added, and that the prepared aqueous solution was stabilized (see Tables 2.3).

That is, the addition of the alcohol makes it possible to prepare a high-concentration aqueous solution even when the amount of the nonionic surfactant added is 1 w / v%, and no precipitation is observed even after two weeks of storage in a refrigerator. Was.

Further, regarding the blending amount of alcohols,
To stabilize the prepared high concentration aqueous solution, azulene
When SO ₃ Na is 2w / v% and 4w / v%, each is about 10w / v%
It is understood that sufficient low-temperature stability is difficult to obtain when the content is less than or equal to about 30 w / v% (Test Nos. 17 and 20).

<Test Example B> Next, in order to evaluate the stability of the aqueous solution using the change in the content of azulene SO ₃ Na as an index, various types of high-purity water were used based on the formulation shown in Table 4 using purified water as a solvent. A concentrated aqueous solution was prepared, passed through a membrane filter, and then filled in a glass container.

These sample solutions were stored for one week at a temperature of 60 ° C., and the azulene SO ₃ Na content in each formulation was measured to examine the stability. The azulene SO ₃ Na content was measured using a spectrophotometer, and the content was calculated from an absorbance value near an absorption maximum wavelength of 570 nm derived from azulene SO ₃ Na.

The test results were as shown in Table 4.

Regarding the effect on the azulene SO ₃ Na content, in the case where only the nonionic surfactant is blended, the azulene SO ₃ Na
Did not contribute to the stabilization, but rather tended to slightly worsen (Test Nos. 28 and 29).

It has been found that the aqueous solution of azulene SO ₃ Na can be remarkably stabilized by adding an alcohol such as glycerin, xitol or ethanol alone or in combination of two or more thereof and at least 17 w / v%. Test No. 31, 32, 33).

From the above test examples, the aqueous solution obtained by blending a nonionic surfactant and alcohols with azulene SO ₃ Na is as follows:
It has been found that it is extremely effective in enhancing the dissolution assisting effect of the nonionic surfactant, stabilizing the aqueous solution, and stabilizing azulene SO ₃ Na.

That is, for preparing an aqueous solution of azulene SO ₃ Na of 1 w / v% or more and stabilizing the aqueous solution, a nonionic surfactant and an alcohol of 17 w / v% or more, preferably
It has been found that the method of blending 0 w / v% or more of alcohols is extremely effective.

Based on these results, in Examples 1 to 8 and Comparative Examples 1 and 2 based on more specific formulations, the conditions of 60 ° C. were used in order to estimate the long-term stability of the formulations. Was stored for 1 to 2 months, and the azulene SO ₃ Na content was measured in the same manner as in the test example in Table 2 to examine the stability.

Example 1 Azulene SO ₃ Na 2 g Glycerin 25 g Sodium citrate 0.2 g Polyoxyethylene (20) sorbitan monolaurate 5 g Ethanol 20 g Perfume 0.2 g Total amount 100 mL Polyoxyethylene (20) sorbitan monolaurate And glycerin was dissolved by heating. Azulene SO ₃ Na
, Sodium citrate, ethanol and fragrance were sequentially mixed and dissolved, made up to 100 mL with purified water, passed through a membrane filter, and filled in a glass container. pH is 7.
It was 6. The residual ratio of azulene SO ₃ Na after storage at 60 ° C. for one month in this preparation was 99%, and the appearance was extremely stable.

<Example 2> Azulene SO ₃ Na 2.5 g Glycerin 40 g Sodium citrate 0.2 g Polyoxyethylene (60) hydrogenated castor oil 5 g Ethanol 14 g Fragrance 0.3 g Total amount 100 mL Polyoxyethylene (60) hydrogenated castor oil And glycerin was dissolved by heating. Azulene SO ₃ Na, sodium citrate, ethanol and fragrance were sequentially mixed and dissolved in this, made up to 100 mL with purified water, and passed through a membrane filter.
Filled into glass containers. pH was 7.8. The residual ratio of azulene SO ₃ Na after storage at 60 ° C. for one month in this preparation was 98%, and the appearance was extremely stable.

Example 3 Potassium Azulene Sulfonate 4 g Glycerin 15 g Sodium Citrate 0.2 g Polyoxyethylene (20) hydrogenated castor oil 5 g Ethanol 14 g Fragrance 0.4 g Total 100 mL Polyoxyethylene (60) hydrogenated castor oil, glycerin Was heated and dissolved. This is potassium azulene sulfonate,
Sodium citrate, ethanol, and flavor were sequentially mixed and dissolved, made up to 100 mL with purified water, passed through a membrane filter, and then filled in a glass container. pH was 7.8. The residual ratio of potassium azulene sulfonate after storage at 60 ° C. for one month in this preparation was 99%, and the appearance was extremely stable.

Example 4 Azulene SO ₃ Na 4 g Glycerin 15 g Disodium phosphate 0.6 g Monosodium phosphate 0.1 g Polyoxyethylene (20) sorbitan monolaurate 3 g Ethanol 30 g L-menthol 5 g Fragrance 0.5 g Total amount 100 mL Polyoxyethylene (20) sorbitan monolaurate and glycerin were heated and dissolved. Azulene SO ₃ Na
, Disodium phosphate, monosodium phosphate, ethanol, L-menthol, and perfume were sequentially mixed and dissolved, made up to 100 mL with purified water, passed through a membrane filter, and filled in a glass container. pH was 7.9.
Azulene SO ₃ N after storage for 1 month at 60 ° C in this formulation
The residual ratio of a was 97%, and the appearance was extremely stable.

Example 5 Azulene SO ₃ Na 4 g Xylitol 10 g Disodium phosphate 0.6 g Monosodium phosphate 0.1 g Polyoxyethylene (20) sorbitan monolaurate 5 g Ethanol 30 g L-menthol 5 g Fragrance 0.5 g Total amount 100 mL Polyoxyethylene (20) sorbitan monolaurate and xylitol were dissolved by heating. Azulene SO ₃ N
a, disodium phosphate, monosodium phosphate, ethanol, L-menthol, and flavor were sequentially mixed and dissolved, made up to 100 mL with purified water, passed through a membrane filter, and filled in a glass container. pH was 7.8.
Azulene SO ₃ N after storage for 1 month at 60 ° C in this formulation
The residual ratio of a was 97%, and the appearance was extremely stable.

Example 6 Azulene SO ₃ Na 4 g Glycerin 35 g Disodium phosphate 1.2 g Monosodium phosphate 0.2 g Polyoxyethylene (20) sorbitan monolaurate 10 g Sodium edetate 0.2 g Ethanol 30 g L- Menthol 5 g Flavor 0.5 g Total amount 100 mL Polyoxyethylene (20) sorbitan monolaurate and glycerin were heated and dissolved. Azulene SO ₃ Na
, Disodium phosphate, monosodium phosphate, sodium edetate, ethanol, L-menthol, and flavor were sequentially mixed and dissolved, made up to 100 mL with purified water, passed through a membrane filter, and filled in a glass container. pH
Was 7.6. The residual ratio of azulene SO ₃ Na after storage at 60 ° C. for one month in this preparation was 97%, and the appearance was extremely stable.

Example 7 Azulene SO ₃ Na 4 g Glycerin 40 g Disodium phosphate 2.5 g Monosodium phosphate 0.2 g Polyoxyethylene (20) sorbitan monolaurate 5 g Sodium edetate 0.2 g Ethanol 30 g L- Menthol 5 g Flavor 0.5 g Total amount 100 mL Polyoxyethylene (20) sorbitan monolaurate and glycerin were heated and dissolved. Azulene SO ₃ Na
, Disodium phosphate, monosodium phosphate, sodium edetate, ethanol, L-menthol, and flavor were sequentially mixed and dissolved, made up to 100 mL with purified water, passed through a membrane filter, and filled in a glass container. pH
Was 7.7. The residual ratio of azulene SO ₃ Na after storage for 2 months at 60 ° C. in this formulation was 99%, and the appearance was extremely stable.

Example 8 Azulene SO ₃ Na 4 g Glycerin 40 g Disodium phosphate 2.5 g Polyoxyethylene (20) sorbitan monolaurate 5 g Sodium edetate 0.5 g Ethanol 30 g L-menthol 5 g Mentha oil 0.5 g Total amount 100 mL Polyoxyethylene (20) sorbitan monolaurate and glycerin were heated and dissolved. Azulene SO ₃ Na
, Disodium phosphate, sodium edetate, ethanol, L-menthol, peppermint oil
It was made up to 100 mL with purified water, passed through a membrane filter, and filled in a plastic container. pH was 7.9. The residual ratio of azulene SO ₃ Na after storage at 60 ° C. for 2 months in this preparation was 100%, and the appearance was extremely stable.

Comparative Example 1 Azulene SO ₃ Na 2 g Glycerin 5 g Disodium phosphate 0.6 g Polyoxyethylene (60) hydrogenated castor oil 10 g Ethanol 5 g Fragrance 0.2 g Total amount 100 mL Polyoxyethylene (60) hydrogenated castor oil Glycerin was dissolved by heating. Azulene SO ₃ Na, disodium phosphate, ethanol and fragrance were mixed and dissolved in this order, made up to 100 mL with purified water, and passed through a membrane filter.
Filled into glass containers. pH was 8.2. As a result of storing this formulation at 60 ° C. for one month, the appearance turned black.

Comparative Example 2 Azulene SO ₃ Na 4 g Glycerin 5 g Sodium citrate 0.2 g Polyoxyethylene (20) sorbitan monolaurate 10 g Ethanol 10 g Perfume 0.4 g Total amount 100 mL Polyoxyethylene (20) sorbitan monolaurate And glycerin was dissolved by heating. Azulene SO ₃ Na
, Sodium citrate, ethanol and fragrance were sequentially mixed and dissolved, made up to 100 mL with purified water, passed through a membrane filter, and filled in a glass container. pH is 7.
It was 8. As a result of storing this formulation at 60 ° C. for one month,
The appearance turned black.

[0066]

Industrial Applicability According to the present invention, it is possible to obtain a high-concentration aqueous solution of azulene having excellent stability, which could not be achieved by the conventional method for stabilizing an azulene sulfonate preparation. It has become possible to provide as a useful medicine having the advantage of ensuring the quality of the product in.

[0067]

[Table 1]

[0068]

[Table 2]

[0069]

[Table 3]

[0070]

[Table 4]

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Mitsuo Tanaka 76, Nishisakuramachi, Minami-ku, Nagoya-shi, Aichi Japan Ophthalmic Research Laboratories

Claims (7)

[Claims] 1. An azulene aqueous solution containing an azulene sulfonate as a medicinal ingredient, wherein a nonionic surfactant and an alcohol are combined as a water-solubility / stability improver for the azulene sulfonate. Azulene aqueous solution characterized by being performed. 2. An azulene aqueous solution containing an azulene sulfonate as a medicinal component, comprising 0.5 to 30 w / v% of a nonionic surfactant and 15 to 85 w / v% of alcohols. Azulene aqueous solution. 3. The nonionic surfactant in an amount of 3 to 15 w / v%.
3. The azulene aqueous solution according to claim 2, comprising 20 to 75% w / v% of alcohol. 4. The nonionic surfactant is one or two or more selected from the group consisting of polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, and polyoxyethylene alkyl ether.
4. The azulene aqueous solution according to claim 3, wherein the aqueous solution is selected from a combination of at least two or more species. 5. The method according to claim 1, wherein the alcohol is selected from one or a combination of two or more selected from aliphatic alcohols having 2 to 4 carbon atoms and polyhydric alcohols having 3 to 6 carbon atoms. The azulene aqueous solution according to claim 3, wherein 6. An azulene sulfonate content of 0.5
The aqueous azulene solution according to any one of claims 1 to 5, wherein the aqueous solution is from 10 to 10 w / v%. 7. An azulene sulfonate content of 1.5
The aqueous solution of azulene according to claim 4, wherein the aqueous solution of the azulene is from 6 to 6% w / v.