JP6571391B2 - Aqueous preparation - Google Patents

Description

The present invention relates to an aqueous preparation that improves the light stability of vitamin B ₁₂ compounds while containing pranoprofen and / or a salt thereof and vitamin B ₁₂ compounds. The present invention also relates to a method for photostabilizing vitamin B ₁₂ in an aqueous preparation containing pranoprofen and / or a salt thereof and vitamin B ₁₂ .

  Planoprofen and / or its salts have the effect of suppressing the biosynthesis of prostaglandins that cause inflammation and pain. In the ophthalmic field, alleviation of symptoms such as redness of the eyes and itching, blepharitis, and conjunctivitis It is widely used for the purpose of prevention or treatment of scleritis including suprasclitis, postoperative inflammation, anterior uveitis, and the like. On the other hand, pranoprofen and / or a salt thereof has a drawback of being easily decomposed when exposed to light in an aqueous preparation. Therefore, an aqueous preparation containing pranoprofen and / or a salt thereof is required to improve the stability of pranoprofen and / or a salt thereof against light.

Conventionally, various preparation techniques for imparting light stability to pranoprofen and / or a salt thereof in an aqueous preparation have been proposed. For example, Patent Document 1, it pranoprofen / or light stabilizing a salt thereof can be achieved disclosed by vitamin B ₁₂ compound. Patent Document 2 discloses that in ophthalmic preparations, precipitation by photodegradation of pranoprofen can be suppressed by blending vitamin B ₂ , vitamin B ₁₂ or vitamin E together with pranoprofen. Patent Document 3 discloses that in the eye drop, light stabilization of pranoprofen can be achieved by blending cyanocobalamin with pranoprofen. Furthermore, Patent Document 4 discloses that in an aqueous liquid preparation, light stabilization of pranoprofen can be achieved by blending bisulfite, berberine, cyanocobalamin, or sodium azulenesulfonate with pranoprofen. Has been.

On the other hand, vitamin B ₁₂ is also known to have pharmacological effects such as improvement of fatigue and eye strain. By combining pranoprofen and / or a salt thereof and vitamin B _{12 in} an aqueous preparation, pranopro und / or with improved light stability of the salt, complex pharmacological action of pranoprofen and / or salts thereof and vitamin B ₁₂ compounds are also expected, it is possible to provide a beneficial formulation. However, conventionally, it has not been studied stability of vitamin B ₁₂ such when allowed to coexist pranoprofen and / or salts thereof and vitamin B ₁₂ compounds in aqueous formulations.

JP 2005-314353 A JP 2005-247799 JP JP 2005-247777 A Japanese Unexamined Patent Publication No. 2005-15368

The present inventors have revealed that studied for practical use of an aqueous formulation comprising pranoprofen and / or salts thereof and vitamin B ₁₂ compound, in an aqueous formulation, vitamin B ₁₂ compounds are pranoprofen and / or Coexisting with the salt faced a new problem of being easily decomposed by light exposure and significantly reducing light stability. Plano in flurbiprofen and / or aqueous formulations comprising that salt and vitamin B ₁₂ compound and vitamin B ₁₂ compound is decomposed are optically unstable, not only the pharmacological action based on vitamin B ₁₂ compound is attenuated, Plano It may also cause a decrease in photostability of profen and / or its salts.

Such a problem of photostabilization of vitamin B ₁₂ has not been grasped in the prior art, and no means for solving it has been clarified. The present invention is in an aqueous formulation comprising pranoprofen and / or salts thereof and vitamin B ₁₂ compound, and an object thereof is to provide a preparation technique for improving the light stability of vitamin B ₁₂ compound.

The present inventors have, as a result of intensive investigation to solve the above problems, in an aqueous formulation comprising pranoprofen and / or salts thereof and vitamin B ₁₂ include, by containing macrogol and / or xanthan gum, vitamins It was found that degradation of B ₁₂ species due to light exposure was suppressed, and light stability was improved. The present invention has been completed by further studies based on such knowledge.

That is, this invention provides the invention of the aspect hung up below.
Item 1. (A) pranoprofen and / or its salt, and (B) vitamin B ₁₂ compound, characterized by containing the (C) macrogol and / or xanthan gum, aqueous formulation.
Item 2. Item 4. The aqueous preparation according to Item 1, wherein the component (B) is cyanocobalamin.
Item 3. Item 3. The aqueous preparation according to Item 1 or 2, wherein the component (C) is macrogol.
Item 4. Item 4. The aqueous preparation according to any one of Items 1 to 3, wherein the component (C) is Macrogol 4000.
Item 5. Item 3. The aqueous preparation according to Item 1 or 2, wherein the component (C) is xanthan gum.
Item 6. Item 6. The aqueous preparation according to any one of Items 1 to 5, wherein the concentration of the component (C) is 0.001 to 10 w / v%.
Item 7. Item 7. The aqueous preparation according to any one of Items 1 to 6, wherein the pH is 5.0 to 9.0.
Item 8. Item 8. The aqueous preparation according to any one of Items 1 to 7, which is an eye drop.
Item 9. (A) pranoprofen and / or a salt thereof, in an aqueous formulation comprising (B) a vitamin B ₁₂ compound, (C) is characterized by blending a macrogol and / or xanthan gum, vitamin B ₁₂ compound Light stabilization method.
Item 10. (A) Plano and flurbiprofen and / or their salts, (B) and vitamin B ₁₂ compound, comprising the step of blending and (C) macrogol and / or xanthan gum, the manufacturing method of the aqueous formulation.

According to the present invention, while contains pranoprofen and / or salts thereof and vitamin B ₁₂ compound, to improve the light stability of vitamin B ₁₂ compound, the content of vitamin B ₁₂ such as stable over time Can be maintained. Further, according to the present invention, since the light stability of vitamin B ₁₂ compound is improved, degradation by light of pranoprofen and / or a salt thereof can be suppressed, pranoprofen and / or salts thereof and vitamin B It can exert a complex pharmacological action by Class ₁₂ .

1. Aqueous preparation of the aqueous formulations according to the invention is characterized (A) and pranoprofen and / or a salt thereof, and (B) vitamin B ₁₂ compounds, that contain the (C) macrogol and / or xanthan gum. Below, the aqueous formulation of this invention is explained in full detail.

In the present invention, the aqueous preparation is a preparation containing water as a base. In this specification, the unit of concentration “w / v%” of each component indicates a mass-to-volume percentage in the 16th revised Japanese Pharmacopoeia and is synonymous with g / 100 mL. In the present invention, the improvement of the light stabilizing or photostability of the vitamin B ₁₂ compound, in an aqueous formulation, vitamin B ₁₂ compound by receiving light exposure in the presence of pranoprofen and / or a salt thereof It means that decomposition of is suppressed.

  The aqueous preparation of the present invention contains pranoprofen and / or a salt thereof (hereinafter sometimes referred to as component (A)). Planoprofen is also known as α-methyl-5H- [1] benzopyrano [2,3-b] pyridine-7-acetic acid, and is a known compound known to have anti-inflammatory activity in the ophthalmic field. .

  The salt of pranoprofen is not particularly limited as long as it is pharmaceutically acceptable. For example, metal salts such as sodium salt, potassium salt, calcium salt, magnesium salt, aluminum salt; triethylamine salt, diethylamine salt, Examples thereof include organic base salts such as morpholine salt and piperazine salt. These pranoprofen salts may be used alone or in combination of two or more.

  In the aqueous preparation of the present invention, one kind selected from pranoprofen and a salt thereof may be used alone, or two or more kinds may be used in combination. Of the pranoprofen and salts thereof, pranoprofen is preferable.

  In the aqueous preparation of the present invention, the concentration of the component (A) is appropriately set according to the use of the aqueous preparation and the like, for example, 0.001 to 0.5 w / v%, preferably 0.01 to 0.2 w / v%, more preferably 0.01 to 0.1 w / v%.

Further, the aqueous preparation of the present invention contains vitamin B ₁₂ (hereinafter sometimes referred to as component (B)). In the aqueous formulations of the present invention, vitamin B ₁₂ compound, together with contributing to the improvement of the light stability of pranoprofen and / or salts thereof, exhibit improving effect of fatigue the eye and eye strain.

Vitamin B ₁₂ is a compound having a structure in which cobalt is coordinated to the choline ring, and specific examples include cyanocobalamin, mecobalamin, hydroxocobalamin, adenosylcobalamin, hydroxocobalamin hydrochloride, and hydroxocobalamin acetate.

In the aqueous preparation of the present invention, vitamin B ₁₂ may be used singly or in combination of two or more. Among the vitamin B ₁₂ compound, from the viewpoint of further improving the effective light stability, preferably cyanocobalamin, mecobalamin, acetate hydroxocobalamin, more preferably include cyanocobalamin.

  In the aqueous preparation of the present invention, the concentration of the component (B) is appropriately set according to the use of the aqueous preparation and the like, for example, 0.0002 to 0.1 w / v%, preferably 0.002 to 0.05 w / v%, more preferably 0.004 to 0.02 w / v%.

Further, the aqueous formulation of the present invention, in addition to the pranoprofen and / or salts thereof and vitamin B ₁₂ compound, macrogol and / or xanthan gum containing (hereinafter, (C) may be referred to as components) . Thus, by including macrogol and / or xanthan gum, degradation due to light exposure of vitamin B ₁₂ caused in the presence of pranoprofen and / or a salt thereof can be suppressed, and light stabilization of vitamin B ₁₂ It becomes possible to improve the property.

Macrogol is a compound also called polyethylene glycol. Macrogoal is macrogol 200, macrogol 300, macrogol 400, macrogol 600, macrogol 1000, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 20000, macrogol depending on the average molecular weight 35000 etc. are known. Any of these macrogols may be used in the aqueous preparation of the present invention, and one of these macrogols may be used alone, or two or more thereof may be used in combination. Among these macrogol, from the viewpoint of more to further effectively improve the light stability of vitamin B ₁₂ compound, preferably macrogol 4000, macrogol 6000, and more preferably include macrogol 4000.

  Xanthan gum is a polysaccharide containing glucose, mannose and glucuronic acid as constituent monosaccharides, and is known to be obtained by fermenting carbohydrates using microorganisms of the genus Xanthomonas.

In the aqueous preparation of the present invention, either macrogol or xanthan gum may be used as the component (C), or these may be used in combination. Among the component (C), from the viewpoint of more to further effectively improve the light stability of vitamin B ₁₂ compound, preferably macrogol alone or in combination of macrogol and xanthan gum and the like.

In the aqueous preparation of the present invention, the concentration of the component (C) is not particularly limited, and may be appropriately set according to the type of the component (C). For example, 0.001 to 10 w / v%, preferably Is 0.005 to 5 w / v%. From the viewpoint of more to further effectively improve the light stability of vitamin B ₁₂ compounds include the range preferred range of concentrations for each type of component (C).
When macrogol is used: preferably 0.005 to 5 w / v%, more preferably 0.01 to 2 w / v%, particularly preferably 0.05 to 1 w / v%.
When xanthan gum is used: preferably 0.005 to 1 w / v%, more preferably 0.02 to 0.5 w / v%, particularly preferably 0.05 to 0.3 w / v%.

  In addition to the components (A) to (C), the aqueous preparation of the present invention may contain a buffering agent in order to provide a buffering action. Although it does not restrict | limit especially as a buffering agent, For example, a boric acid buffer, a phosphate buffer, a citrate buffer, a tartaric acid buffer, an acetic acid buffer, a Tris buffer, an amino acid (glutamic acid etc.) etc. are mentioned. These buffering agents may be used alone or in combination of two or more. Among these buffering agents, boric acid buffering agents (boric acid and borax) have a buffering ability in a pH range where pranoprofen and / or a salt thereof can be dissolved, and are preferably used in the present invention. The

  In the aqueous preparation of the present invention, the concentration of the buffer may be appropriately set within a range in which a desired buffer action can be imparted depending on the type of buffer used, for example, 0.001 to 5 w / v%, Preferably it is 0.05-3 w / v%, More preferably, 0.1-2 w / v% is mentioned.

  In addition to the above components, the aqueous preparation of the present invention may contain a pharmacological component depending on the use of the aqueous preparation. The pharmacological component to be used is not particularly limited. Vitamins, amino acids, anti-cataract agents, angiogenesis inhibitors, immunosuppressants, protease inhibitors, aldose reductase inhibitors, antihistamines, antiallergic agents, anxiety agents, antipsychotics, antibiotics, antitumor agents, Antihyperlipidemic drugs, antitussives / an expectorants, muscle relaxants, antiepileptic drugs, antiulcer drugs, antidepressants, cardiotonic drugs, arrhythmia drugs, vasodilators, hypertensive diuretics, diabetes drugs, antituberculosis drugs , An anesthetic antagonist, a skin disease drug, a dental and oral drug, a diagnostic drug, a public health drug and the like can be appropriately selected and used.

  Among these pharmacological components, in the case of a preparation used in the ophthalmic or otolaryngological field such as eye drops, eye wash, nasal drops, ear drops, etc., specifically, epsilon aminocaproic acid, bromfenac, ketorolactolome Anti-histamines such as diphenhydramine hydrochloride; ketotifen fumarate, acitazanolast, amlexanox, pemiro, anti-histamines such as tamine, nepafenac, berberine chloride, berberine sulfate, azulene sulfonate, zinc sulfate, zinc lactate, lysozyme hydrochloride Antiallergic agents such as last potassium, tranilast, ibudilast; antibacterial agents such as norfloxacin, ofloxacin, lomefloxacin, levofloxacin, gentamicin, gatifloxacin; ascorbic acid, flavin adenine dinucleotide sodium, pyridoxyl Vitamins such as hydrochloride, tocopherol acetate, retinol acetate, retinol palmitate, panthenol, calcium pantothenate, sodium pantothenate; amino acids such as aspartic acid, taurine, sodium chondroitin sulfate; neostigmine methyl sulfate, etc. Anti-cholinesterase agents; vasoconstrictors such as naphazoline, tetrahydrozoline, epinephrine, ephedrine, phenylephrine, dl-methylephedrine; keratoconjunctival epithelial disorders such as sodium hyaluronate; sulfadiazine, sulfisoxazole, sulfisomidine, sulfadimethoxine, Famethoxypyridazine, sulfamethoxazole, sulfaethidol, sulfamethomidine, sulfaphenazole, sulfo Aguanijin, phthalidyl Rusuru phosphatidyl azole, sulfa drugs such as succinyl Rusuru phosphatidyl azoles and the like. The compounds exemplified herein may be in the form of a salt or other salt as long as they are pharmaceutically acceptable.

  About content of these pharmacological components, it sets suitably according to the kind of pharmacological component, the use of a liquid agent, etc.

  In addition to the above components, the liquid agent used in the present invention, if necessary, isotonic agents, solubilizers, viscous bases, chelating agents, cooling agents, pH adjusters, preservatives, You may contain additives, such as a stabilizer and surfactant.

  Examples of the isotonic agent include saccharides such as sorbitol, glucose and mannitol; polyhydric alcohols such as glycerin and propylene glycol; salts such as sodium chloride; boric acid and the like. These isotonic agents may be used alone or in combination of two or more.

  Examples of the solubilizer include nonionic surfactants such as polyoxyethylene sorbitan monooleate, polyoxyethylene hydrogenated castor oil, tyloxapol, and pluronic; and polyhydric alcohols such as glycerin. These solubilizers may be used alone or in combination of two or more.

  Examples of the viscous base include water-soluble polymers such as polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, carboxyvinyl polymer, sodium chondroitin sulfate, alginic acid or a salt thereof, sodium hyaluronate; hypromellose, hydroxyethylcellulose, methylcellulose, hydroxypropyl Examples thereof include celluloses such as cellulose, hydroxypropylmethylcellulose, and sodium carboxymethylcellulose. These viscous bases may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the chelating agent include edetate, citric acid or a salt thereof. These chelating agents may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the refreshing agent include l-menthol, borneol, camphor, and eucalyptus oil. These refreshing agents may be used alone or in combination of two or more.

  Examples of the pH adjuster include alkalis such as sodium hydroxide, potassium hydroxide and borax; acids such as acetic acid, citric acid, hydrochloric acid, phosphoric acid, tartaric acid and boric acid.

  Examples of the preservative include sorbic acid or a salt thereof, benzoic acid or a salt thereof, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, chlorobutanol, chlorhexidine gluconate, boric acid, dehydroacetic acid or a salt thereof Benzalkonium chloride, benzethonium chloride, benzyl alcohol, zinc chloride, parachlormetaxylenol, chlorcresol, phenethyl alcohol, polydronium chloride, thimerosal, polyhexamethylene biguanide and the like. These preservatives may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the stabilizer include polyvinyl pyrrolidone, sulfite, monoethanolamine, glycerin, propylene glycol, cyclodextrin, dextran, ascorbic acid, edetate, taurine, tocopherol and the like. These stabilizers may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the surfactant include nonionic surfactants such as tyloxapol, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene block copolymer, polyoxyethylene sorbitan fatty acid ester, octoxynol; alkyldiaminoethylglycine, Amphoteric surfactants such as lauryldimethylaminoacetic acid betaine; anionic surfactants such as alkyl sulfate, N-acyl taurate, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl ether sulfate; alkyl pyridinium salts; And cationic surfactants such as alkylamine salts. These surfactants may be used individually by 1 type, and may be used in combination of 2 or more type.

  About the density | concentration of these additives, it sets suitably according to the kind of additive, the use of an aqueous formulation, etc.

  The use of the liquid preparation used in the present invention is not particularly limited, and examples thereof include pharmaceuticals and contact lens care products. Specific examples of pharmaceuticals include ophthalmic solutions such as eye drops (including eye drops for contact lenses that can be instilled even when wearing contact lenses), eye wash, etc .; ophthalmic and nasal solutions such as nasal drops and ear drops An internal preparation, an injection, an external preparation and the like. Specific examples of contact lens care products include contact lens mounting liquids, contact lens multipurpose solutions, and the like. Among the uses of these solutions, preferably, ophthalmic solutions, otolaryngological solutions, and contact lens care products, and more preferably eye drops.

  The form of the aqueous preparation of the present invention is not particularly limited as long as it contains water as a base. For example, it may be in the form of an aqueous solution, a suspension, an emulsion, etc., preferably an aqueous solution. .

  In addition, the pH of the aqueous preparation of the present invention is not particularly limited and may be appropriately set according to the use of the aqueous preparation, for example, 5.0 to 9.0, preferably 5.5 to 8. 5, More preferably, 6.5-8.5, More preferably, 7.0-8.0 is mentioned.

  The use of the aqueous preparation of the present invention is not particularly limited, and examples thereof include pharmaceuticals and contact lens care products. Specific examples of pharmaceuticals include ophthalmic solutions such as eye drops (including eye drops for contact lenses that can be instilled even when wearing contact lenses), eye wash, etc .; ophthalmic and nasal solutions such as nasal drops and ear drops An internal preparation, an injection, an external preparation and the like. Specific examples of contact lens care products include contact lens mounting liquids, contact lens multipurpose solutions, and the like. Among these aqueous preparations, ophthalmic solutions, otolaryngological solutions, and contact lens care products are preferable, and eye drops are more preferable.

  The aqueous preparation of the present invention may be produced according to a known preparation method depending on the form, use, etc., and can be prepared, for example, by blending each component with an aqueous base such as water or physiological saline. For example, in the case of a medicine, it can be produced using the method described in the 16th revised Japanese Pharmacopoeia General Rules for Preparations.

2. Light stabilization method The present invention also, (A) pranoprofen and / or a salt thereof, in an aqueous formulation comprising (B) a vitamin B ₁₂ compound, blending the (C) macrogol and / or xanthan gum A method for photostabilizing vitamin B ₁₂ is provided. The light stabilization method is useful for improving the light stability of vitamin B ₁₂ in an aqueous preparation containing (A) pranoprofen and / or a salt thereof and (B) vitamin B ₁₂ .

In light stabilizing method of the present invention, pranoprofen and / or a pharmaceutically acceptable type and concentration type and concentration of vitamin B ₁₂ such salts, macrogol and / or xanthan gum type and concentration used, The types of pharmacological components and additives incorporated in the aqueous preparation, the pH of the aqueous preparation, the preparation form and use of the aqueous preparation, and the like are as described in the section “1. Aqueous preparation”.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples. In the following test examples, pranoprofen was manufactured by API Corporation, cyanocobalamin was manufactured by DMS Nutrition Japan, macrogol was made by NOF's Macrogol 4000, and xanthan gum was Echogum T made by DSP Gokyo Food & Chemical. In Test Example 3, the test was conducted on a different day from Reference Test Example 1 and Test Examples 1 and 2.

Reference test example 1
An aqueous preparation was prepared by mixing each component shown in Table 1 by a conventional method. 5 ml of the obtained aqueous preparation was filled into a 5 ml capacity colorless and transparent glass ampule, and placed in a light stability test apparatus (LT-120A-WCD, manufactured by Nagano Science Co., Ltd.) having an illuminance set to 3,000 lx. It was stored until the total illuminance reached 600,000 lx · hr. The concentration of vitamins in the aqueous preparation before and after storage was measured by liquid chromatography, and the residual ratio (%) of vitamins was calculated according to the following formula.

The obtained results are shown in Table 1. For flavin adenine dinucleotide sodium, pyridoxine hydrochloride, and panthenol, the presence or absence of pranoprofen did not significantly affect the residual rate (Reference Examples 1 to 6). On the other hand, cyanocobalamin was extremely excellent in photostability in the absence of pranoprofen, but the residual ratio after storage was greatly reduced in the presence of pranoprofen (Reference Examples 7 and 7). Comparative Example 1). From these results, it has been clarified that vitamin B ₁₂ has a characteristic that, unlike the other vitamins, in the presence of pranoprofen, the photostability is remarkably lowered and easily decomposed.

Test example 1
An aqueous preparation was prepared by mixing each component shown in Table 2 by a conventional method. With respect to the obtained aqueous preparation, the residual ratio of cyanocobalamin after storage was determined in the same manner as in Reference Test Example 1 except that the total illuminance was changed to 400,000 lx · hr.

  The obtained results are shown in Table 2. From this result, it is clear that when macrogol or xanthan gum is contained in an aqueous preparation containing pranoprofen and cyanocobalamin, the residual ratio of cyanocobalamin is significantly increased and the photostability of cyanocobalamin is significantly improved. (Examples 1 and 2). In particular, when macrogol was used, it was revealed that the photostability of cyanocobalamin in the presence of pranoprofen was dramatically improved (Example 1). On the other hand, when hydroxyethyl cellulose was used, it hardly affected the light stability of cyanocobalamin in the presence of pranoprofen (Comparative Example 2). When sodium hyaluronate, neostigmine methyl sulfate, or taurine was used, the photostability of cyanocobalamin in the presence of pranoprofen was reduced (Comparative Examples 3 to 5).

Test example 2
An aqueous preparation was prepared by mixing each component shown in Table 3 by a conventional method. With respect to the obtained aqueous preparation, the residual ratio of cyanocobalamin after storage was determined in the same manner as in Reference Test Example 1 except that the total illuminance was changed to 400,000 lx · hr.

  The obtained results are shown in Table 3. From this result, 0.05 to 1 w / v% macrogol or 0.05 to 0.3 w / v% xanthan gum can effectively improve the photostability of cyanocobalamin in the presence of pranoprofen. (Examples 1 to 9).

Test example 3
An aqueous preparation was prepared by mixing each component shown in Table 4 by a conventional method. With respect to the obtained aqueous preparation, the residual ratio of cyanocobalamin after storage was determined in the same manner as in Reference Test Example 1 except that the total illuminance was changed to 400,000 lx · hr.

Table 4 shows the obtained results. From this result, it was confirmed that the photostability of cyanocobalamin was improved by macrogol and / or xanthan gum within the pH range normally employed in ophthalmic solutions and contact lens care products (Example 10). ~ 22). Furthermore, it was also confirmed that the light stability of cyanocobalamin was significantly improved by using together macrogol and xanthan gum (Example 22).

Claims (7)

(A) pranoprofen and / or its salt, and (B) vitamin B ₁₂ compound, characterized by containing the (C) macrogol and / or xanthan gum, aqueous formulation.   The aqueous preparation according to claim 1, wherein the component (B) is cyanocobalamin.   The aqueous preparation according to claim 1 or 2, wherein the component (C) is macrogol.   The aqueous preparation according to any one of claims 1 to 3, wherein the component (C) is Macrogol 4000.   The aqueous preparation according to any one of claims 1 to 4, wherein the concentration of the component (C) is 0.001 to 10 w / v%.   The aqueous preparation according to any one of claims 1 to 5, which is an eye drop. (A) pranoprofen and / or a salt thereof, in an aqueous formulation comprising (B) a vitamin B ₁₂ compound, (C) is characterized by blending a macrogol and / or xanthan gum, vitamin B ₁₂ compound Light stabilization method.