JP2016065088A - Medicinal preparation containing tranilast in transparent package - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medicinal preparation in a transparent package in which tranilast is contained and is visually recognizable inside but decomposition of tranilast by light is suppressed.SOLUTION: There is provided a medicinal preparation in a transparent package in which the medicinal preparation containing tranilast or its salt is contained in the transparent package provided with light shielding means to shield it from light with a wavelength of 350-450 nm.SELECTED DRAWING: None

Description

The present invention relates to a pharmaceutical preparation containing a transparent package. More specifically, the present invention relates to a pharmaceutical preparation containing a transparent package in which tranilast is contained in a package capable of visually recognizing the inside and suppressing degradation of tranilast by light. The present invention also relates to a method for suppressing photolysis of tranilast.

Tranilast (N- (3,4-dimethoxycinnamoyl) anthranilic acid) is used as an orally administered agent for bronchial asthma and allergic rhinitis as a therapeutic agent for allergic diseases. Furthermore, tranilast is now used as an active ingredient in eye drops for allergic diseases. In general, tranilast is extremely unstable to light, so it is very important to ensure the stability of the formulation against exposure to light during manufacture and after opening. Normally, in order to stably store a preparation containing a pharmacologically active substance that is unstable to light, the preparation is filled in a brown or aluminum container, or stored in a paper box or a plastic storage bag that does not transmit light. The device has been devised to be portable.

By the way, in pharmaceutical preparations such as eye drops, eyewashes and injections, the foreign substance confirmation test is regulated in the quality control in the Pharmaceutical Affairs Law (by the Japanese Pharmacopoeia), and the container of the pharmaceutical preparation is a transparent package that allows the inside to be observed ( Container). In addition, even for a preparation without such a regulation, it is desirable for a user to have a package (container) having transparency that allows the inside to be observed with the naked eye for confirmation of the remaining amount. .

Conventionally, in a pharmaceutical preparation containing tranilast contained in a container, a brown container has been adopted in order to provide both the light stability of tranilast in the container and the visibility inside the container. However, the conventional brown container has a problem that the stability of tranilast cannot be sufficiently ensured. In addition, in a container that can substantially block light, such as an aluminum container or an opaque container, the properties and internal volume of the internal preparation cannot be confirmed, resulting in inconvenience in manufacturing process management and quality control.
Furthermore, the method of carrying and storing the tranilast-containing pharmaceutical preparation in a container in a paper box that does not transmit light or a plastic storage bag and carrying and storing it is extremely inconvenient for the user even if the stability of tranilast can be ensured. On the other hand, for example, in Patent Documents 1 and 2, from the viewpoint of pharmaceutical formulation,
A method for improving the photostability of a drug has been proposed, but no means for stably holding a drug against light by modifying a package that contains the drug is disclosed.

Against the background of such prior art, it has been desired to develop a pharmaceutical preparation containing a package containing tranilast in a package capable of visually recognizing the inside and suppressing the degradation of tranilast by light.

JP-A-63-215642 JP 2003-265575 A

The object of the present invention is to solve the above-mentioned problems of the prior art. Specifically, an object of the present invention is to provide a pharmaceutical preparation containing a transparent package containing tranilast in a package capable of visually recognizing the inside and suppressing degradation of tranilast by light. The present invention also provides:
It aims at providing the method of suppressing decomposition | disassembly by light of tranilast.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the decomposition of tranilast by light can be suppressed by blocking light having a wavelength of 350 to 450 nm.
The present invention has been completed by further studies based on this finding.

That is, the present invention is a pharmaceutical preparation containing a transparent package described below:
Item 1. A pharmaceutical preparation containing a transparent package, wherein the pharmaceutical preparation containing tranilast or a salt thereof is placed in a transparent package that blocks light having a wavelength of 350 to 450 nm.
Item 2. Item 2. The pharmaceutical preparation containing a transparent package according to Item 1, wherein the transparent package has an average light transmittance of 20% or less in a wavelength region of 350 to 450 nm.
Item 3. Item 3. The pharmaceutical preparation containing a package according to Item 1 or 2, wherein the pharmaceutical preparation is a liquid.
Item 4. Item 4. The pharmaceutical preparation containing a transparent package according to any one of Items 1 to 3, wherein the pharmaceutical preparation is an eye drop, an eye wash, an injection, an external preparation for skin, a nose drop, or a contact lens preparation.

The present invention is also a method for inhibiting photolysis of anthranilic acid derivatives listed below:
Item 5. A method for suppressing the degradation of tranilast or a salt thereof by light, wherein the pharmaceutical preparation containing tranilast or a salt thereof is contained in a transparent package that blocks light having a wavelength of 350 to 450 nm. Method.

Hereinafter, the present invention will be described in detail. In the present specification, the aqueous preparation (or aqueous composition) contains at least 5% by weight, preferably 20% by weight or more, more preferably 50% by weight or more of water in the preparation (or composition). Means things.

The pharmaceutical preparation containing a transparent package of the present invention comprises a pharmaceutical preparation containing tranilast having a wavelength of 350
A light beam of ˜450 nm is accommodated in a transparent transparent packaging body.

Tranilast which is a component contained in the pharmaceutical preparation with a transparent package of the present invention is N- (3,4-
Dimethoxycinnamoyl) anthranilic acid.

In the pharmaceutical preparation containing a transparent package of the present invention, a salt of tranilast can be used instead of or in combination with the above tranilast. The salt of tranilast is not particularly limited as long as it is pharmaceutically acceptable. For example, salts with inorganic salts such as sodium salt and potassium salt, or organic amines such as morpholine, piperazine, piperidine and pyrrolidine. And salts with amino acids. These tranilast pharmaceutically acceptable salts may be used alone or in any combination of two or more.

In the present invention, the pharmaceutical preparation accommodated in the transparent package is not particularly limited as long as it contains tranilast or a salt thereof, and may be composed only of tranilast or a salt thereof, or tranilast or a salt thereof. In addition to the salt, it may contain a pharmaceutically (pharmaceutically) acceptable base or carrier, or other additives.

The concentration of tranilast or a salt thereof in the pharmaceutical preparation contained in the transparent package varies depending on the use and dosage form of the preparation. For example, in the preparation administered orally, the daily dose is 50 to 500.
In the case of a pharmaceutical preparation for topical administration in mg, the formulation can be appropriately designed so that the daily dose is 0.01 to 50 mg. For example, when used as an aqueous preparation, tranilast or a salt thereof is 0.01 to 20% by weight, preferably 0.01 to 10% by weight, more preferably 0.1 to 5% by weight based on the total weight of the preparation. % Can be mentioned.

In addition to the above tranilast or a salt thereof, a compound that imparts light stability to tranilast is added to the preparation contained in the transparent package, so that the stability of tranilast or a salt thereof against light can be obtained from the viewpoint of the formulation. Can be improved.

Examples of the compound that imparts light stability to tranilast include berberine, flavin adenine dinucleotide, hesperidin, oxyquinoline, cyanocobalamin, derivatives thereof, and salts thereof. Specifically, berberine, a salt thereof (eg, berberine chloride, berberine sulfate, etc.) and a derivative thereof (eg, berberine tannate)
(Hereinafter also referred to as berberines); flavin adenine dinucleotide, its salt (
For example, flavin adenine dinucleotide sodium, etc.) and derivatives thereof (hereinafter also referred to as FADs); hesperidin, salts thereof and derivatives thereof (eg, methyl hesperidin, etc.) (hereinafter also referred to as hesperidins); oxyquinoline, Salt or derivative (
For example, oxyquinoline sulfate (hereinafter also referred to as oxyquinolines); and cyanocobalamin, salts thereof and derivatives thereof (hereinafter also referred to as cyanocobalamins).
Can be illustrated. These compounds are known, and may be synthesized by known methods or obtained as commercial products.

Moreover, the said compound can be used even if it is not necessarily a refine | purified state, if it is pharmacologically acceptable. For example, if berberine is used, an extract or extract of herbal medicines such as buckwheat or auren containing these compounds may be used.

The above compounds that impart light stability to tranilast may be used alone or in combination.
Species or more may be used in any combination.

When compounding the above compound that imparts light stability to tranilast in a pharmaceutical preparation contained in a transparent package, the blending ratio of tranilast or a salt thereof and the above compound that imparts light stability to tranilast is used. As an example, the compound that imparts light stability to tranilast is 0.01 to 1000 parts by weight, preferably 0.05 to 500 parts by weight, based on 100 parts by weight of tranilast or a salt thereof. Part, more preferably 0.1 to 300 parts by weight, particularly preferably about 0.2 to 100 parts by weight. More specifically, as a compounding ratio of the above compound that imparts light stability to tranilast to 100 parts by weight of tranilast or a pharmaceutically acceptable salt thereof, 0.1 to 100 parts by weight in the case of berberine 0.1-20 parts by weight, more preferably 0.1-10 parts by weight; in the case of FADs, 0.2-100 parts by weight, preferably 0
. 2 to 20 parts by weight; more preferably 0.2 to 5 parts by weight; in the case of hesperidins,
0.02 to 1000 parts by weight, preferably 0.2 to 1000 parts by weight, more preferably 2 to 1
000 parts by weight; in the case of oxyquinolines, 0.02 to 500 parts by weight, preferably 0.2 to 500 parts by weight, more preferably 0.2 to 50 parts by weight; and in the case of cyanocobalamins 0.5 to 500 parts by weight, preferably 2 to 500 parts by weight, more preferably 4
The range which becomes -500 weight part, More preferably, it becomes 20-500 weight part can be illustrated.

The compounding ratio of the above compound that imparts light stability to tranilast in a pharmaceutical preparation contained in a transparent package varies depending on the type of the compound, the compounding ratio of tranilast, the form of the preparation, etc. If present, the proportion of the above compound that imparts light stability to tranilast in the total weight of the preparation may be 0.00005 to 2% by weight, preferably 0.0005 to 1% by weight. More specifically, if the pharmaceutical preparation contained in the container is an aqueous preparation, when berberine is added to the total weight of the preparation,
5 to 0.5% by weight, preferably 0.00005 to 0.1% by weight; when blending FADs, 0.0001 to 0.5% by weight, preferably 0.001 to 0.1% by weight, Preferably 0.001 to 0.005 wt%; when blended with hesperidins, 0.0001 to 2 wt%, preferably 0.0001 to 1 wt%; when blended with oxyquinolines, 0.000
1 to 1% by weight, preferably 0.0001 to 0.5% by weight; and when blending cyanocobalamin, 0.0001 to 0.5% by weight, preferably 0.0001 to 0.1% by weight, more preferably Is a ratio of 0.001 to 0.5% by weight, more preferably 0.01 to 0.5% by weight, particularly preferably 0.02 to 0.5% by weight or 0.1 to 0.5% by weight. Illustrated.

Moreover, you may mix | blend a solubilizing agent with the pharmaceutical formulation accommodated in a transparent package as needed. In particular, when preparing a pharmaceutical preparation as an aqueous preparation, it is desirable to incorporate a solubilizing agent. Such solubilizers include organic amines such as trometamol, monoethanolamine, diethanolamine, and triethanolamine; surfactants such as polyvinylpyrrolidone and polysorbate; polyhydric alcohols such as propylene glycol; and xanthine derivatives such as caffeine. It is done. In particular, polyvinylpyrrolidone, caffeine, trometamol, monoethanolamine, diethanolamine, and triethanolamine are preferable because the light stability improving effect of tranilast by the above-described compound that imparts light stability to tranilast is enhanced. These solubilizing agents may be used alone or in any combination of two or more.

In the case of blending a solubilizing agent, the blending ratio of the solubilizing agent in the pharmaceutical preparation is usually 0.001 to 10% by weight, preferably 0.05 to 10% by weight in the case of an aqueous preparation. A proportion of 0.1 to 5% by weight is exemplified.

Moreover, the stability with respect to the light of tranilast or its salt can be improved more effectively by mix | blending a specific nonionic surfactant with the pharmaceutical formulation accommodated in a transparent package. Such nonionic surfactants include polyoxyethylene (hereinafter also referred to as POE) -polyoxypropylene (hereinafter also referred to as POP) block copolymers (for example, polyoxyethylene (196) polyoxypropylene (67) glycol ( Poloxamer 407), Poloxamer 235
, Poloxamer 188 etc.); monolauric acid POE (20) sorbitan (polysorbate 20),
POE sorbitan fatty acid esters such as monooleic acid POE (20) sorbitan (polysorbate 80); POE (60) castor oil, polyoxyethylene oxystearic acid triglyceride (60E.O.) (POE (60) hydrogenated castor oil), etc. POE castor oil or hydrogenated castor oil; POE (9)
POE alkyl ethers such as lauryl ether; POE / POP alkyl ethers such as POE (20) POP (4) cetyl ether; and POE alkyl phenyl ethers such as POE (10) nonylphenyl ether. The number in parentheses is the number of moles added (
Average number of moles added). These nonionic surfactants can be used alone or in combination of two or more. Among the nonionic surfactants, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil or polyoxyethylene hydrogenated castor oil is preferable. Above all, POE
(60) hydrogenated castor oil, polysorbate 80, and poloxamer 407 are particularly preferred.

If the content of the nonionic surfactant in the pharmaceutical preparation is an aqueous preparation,
Usually, 0.001-1% by weight, preferably 0.01-1% by weight, based on the total weight of the preparation,
More preferably, it is about 0.05 to 1% by weight.

In addition, when further combined with a chelating agent in the pharmaceutical preparation contained in the transparent package,
From the viewpoint of formulation, it is possible to impart more excellent light stability to tranilast or a salt thereof. Examples of the chelating agent include edetic acid (ethylenediaminetetraacetic acid, EDTA).
, Ethylenediaminediacetic acid (EDDA), diethylenetriaminepentaacetic acid (DTPA), N
-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), N- (2-hydroxyethyl) iminodiacetic acid (HIDA), citric acid, tartaric acid, phosphoric acids (polyphosphoric acid, hexametaphosphoric acid, metaphosphoric acid), succinic acid, Examples thereof include trihydroxymethylaminomethane, nitrilotriacetic acid, 1-hydroxyethane-1,1-diphosphonic acid and the like. These chelating agents can be used alone or in combination, and may be used as pharmacologically or physiologically acceptable salts. Preferred chelating agents are ethylenediaminetetraacetic acid, citric acid and salts thereof. Particularly preferred chelating agents are ethylenediaminetetraacetic acid or a salt thereof,
For example, disodium ethylenediaminetetraacetate, disodium ethylenediaminetetraacetate
Such as dihydrate (sodium edetate).

The compounding ratio of the chelating agent is, for example, about 0.1 with respect to 1 part by weight of the total amount of tranilast or a salt thereof.
0001-10 parts by weight, preferably 0.001-10 parts by weight, more preferably 0.001
˜1 part by weight, particularly preferably about 0.01 to 1 part by weight. Moreover, as a compounding quantity in the pharmaceutical formulation of a chelating agent, this chelating agent is 0.001-1.0 weight% normally with respect to the total weight of this formulation, Preferably it is 0.001-0.5. % By weight, more preferably 0.
For example, about 005 to 0.3% by weight.

In addition, when the pharmaceutical preparation contained in the transparent package is an aqueous preparation, a specific buffer is added to the preparation in place of or in combination with the chelating agent, so that tranilast or a salt thereof can be obtained from the viewpoint of preparation formulation. , Can provide better light stability. Such buffering agents include borate buffering agents, phosphate buffering agents, carbonate buffering agents and the like. Of these, borate buffer and phosphate buffer are preferable. When a buffering agent is blended, the ratio of the buffering agent contained in the preparation is usually 0.0001 to 10% by weight, preferably 0.001 to 5% by weight, more preferably 0. 0% by weight as the total concentration of the buffering agent. An example is 01 to 5% by weight, particularly preferably about 0.1 to 3% by weight.

When the pharmaceutical preparation contained in the transparent package is an aqueous preparation, the pH is usually in the range of pH 4 to 9, preferably from pH 6 to pH 6 from the viewpoint of maintaining good light stability of tranilast or a salt thereof.
The pH is 8.5, more preferably pH 7 to 8.5, particularly preferably pH 7 to 8. In the case of an aqueous preparation, the osmotic pressure is usually in the range of 0.3 to 4.1 as the osmotic pressure ratio with respect to physiological saline,
It is preferably 0.3 to 2.1, particularly preferably about 0.5 to 1.4.

The pharmaceutical preparation used in the present invention can be combined with various carriers (aqueous carrier such as water, hydrophilic carrier, oily carrier, liquid carrier, granular carrier, etc.) in various forms according to the purpose, for example, It can be prepared into dosage forms such as solid preparations, semi-solid preparations, and liquid preparations. Specifically, solid preparations (tablets, powders, granules, capsules, dry syrups, etc.), semi-solid preparations (ointments (hard ointments, ointments etc.), creams etc.), liquid preparations (eye drops, lotions) Preparations, extracts, suspensions, emulsions, syrups, injections (including injections prepared at the time of use), aerosols, soft capsules, drinks, etc.]. In particular, in the present invention, in view of the effect of the present invention that the destabilization of tranilast caused by exposure to light in an aqueous solution can be effectively suppressed, an aqueous formulation is preferred as the pharmaceutical formulation used in the present invention. Can be mentioned. Examples of such an aqueous preparation include a liquid agent and a semi-solid preparation containing water.

The pharmaceutical preparation used in the present invention may be an injection, a suppository, an internal medicine, an inhalation preparation, etc.
It may also be a locally applied pharmaceutical preparation that is easily exposed to light when applied to a patient.
In addition to skin application, mucous membranes that easily feel irritation (corneal and conjunctival ocular mucosa, gums, tongue,
It may be a pharmaceutical preparation applied to the lips, oral mucosa, nasal mucosa, pharyngeal mucosa and the like. For example, as an example of the pharmaceutical preparation used in the present invention, an external preparation for skin (ointment for skin, cream for skin, liquid for skin), eye drop (eye drop), eye wash (eye wash), eye ointment, contact Examples include lens mounting solutions, contact lens preparations (cleaning solution, preservative solution, disinfecting solution, multipurpose solution, etc.), nasal drops (nasal drops), nasal cleaning solutions, oropharyngeal drugs, mouth rinses, ear drops and the like. In this specification, the contact lens includes all types of contact lenses such as hard contact lenses (including oxygen permeable hard contact lenses) and soft contact lenses. Among these, Preferably, an eye drop (eye drop), an eye wash (eye wash), an injection, a skin external preparation, a nose drop, and a contact lens preparation can be mentioned.

In particular, it is possible to examine the presence of foreign substances by visually observing the pharmaceutical preparation in the container from the outside, and it is possible to suitably carry out the provisions of the general preparations of eye drops and the insoluble foreign substance inspection method for injections in the Japanese Pharmacopoeia In view of the effects of the present invention, preferred pharmaceutical preparations include, for example, eye drops, eyewashes,
An injection etc. can be mentioned. In addition, a preparation containing a plurality of doses is preferable because the user can visually recognize the remaining amount of the preparation for each use. Specific examples of the preparation containing multiple doses include eye drops, eye washes, external preparations for skin, nasal drops, and contact lens preparations.

As long as the effects of the present invention are not impaired, the pharmaceutical preparation used in the present invention may contain various components (including pharmacologically active components and physiologically active components) in combination with the above-described components. The type of such components is not particularly limited, and examples thereof include a decongestant component, an eye regulator component, an anti-inflammatory component, an astringent component, an antihistamine component, an antiallergic component, an antipyretic analgesic component, and a stomachic component. , Digestive component, gastric mucosa repair component, ulcer treatment component, antitumor component, local anesthetic component,
Glaucoma treatment ingredient, cataract treatment ingredient, vitamins, amino acids, antibacterial ingredient, bactericidal ingredient,
Examples include saccharides, polysaccharides or derivatives thereof, cellulose or derivatives thereof or salts thereof, water-soluble polymers other than those described above, steroid components, hormones, proteins, peptides, and the like.

Further, the pharmaceutical preparation used in the present invention, if necessary, within a range not impairing the effects of the invention,
Depending on the form of the preparation, various components and additives used for pharmaceuticals, quasi-drugs, and the like are arbitrarily selected and used in combination. Examples of these components or additives include aqueous solvents, thickeners, saccharides, surfactants, preservatives, bactericides, antibacterial agents, isotonic agents, binders commonly used in the preparation of various preparations. And various additives such as excipients, lubricants, disintegrants, ointment bases, gel bases, oily bases, suspending agents, emulsifiers, fragrances or refreshing agents, chelating agents, buffering agents, etc. Can do.

In the present invention, the container containing the pharmaceutical preparation is a transparent package that blocks light having a wavelength of 350 to 450 nm.

The package referred to in the present invention contains not only a package directly containing the above composition (hereinafter referred to as a primary package) but also a packaged composition contained in the package, A package (hereinafter referred to as a secondary package) for packaging the preparation in double or more is also included.

In the present invention, in the case of a packaged composition having a secondary package, at least one package of the primary package and the secondary package may block the light beam. From the viewpoint of suppressing the decomposition of tranilast or a salt thereof in the package not only during distribution and storage, but also in use, it is desirable that the primary package block the light beam.

The form of the package is not particularly limited as long as the pharmaceutical preparation can be accommodated, and can be appropriately selected and set according to the form and use of the pharmaceutical preparation to be accommodated, the primary package or the secondary package, and the like. As an example of the form of the package, in the case of a primary package, a sachet type (small bag type) packaging bag, a tube-shaped container, a bottle-shaped container, PTP packaging, an eye drop container, and the like can be given. Moreover, in the case of a secondary package, a pillow packaging bag etc. are illustrated.

The transparent package referred to in the present invention is a package having internal visibility (transparency) such that the inside can be observed with the naked eye. Specifically, as a transparent package, the average light transmittance in the visible light region of 455 to 780 nm (hereinafter referred to as the average light transmittance in the visible light region of 455 to 780 nm) is 30% or more, preferably 40 %, More preferably 50% or more, particularly preferably 70% or more. By providing the average light transmittance in the visible light region of 455 to 780 nm, it is advantageous in that the visibility inside the package can be ensured. In the present invention, the light transmittance measurement method conforms to the method defined in JIS K7150. The average transmittance in the visible light region of 455 to 780 nm is, for example, 4
It can obtain | require by measuring light transmittance every 5 nm between 55-780 nm, and calculating those average values from each obtained light transmittance.

In the present invention, if the above-mentioned internal visibility (transparency) is ensured in at least a part of the package, the preparation in the package can be visually recognized, so the internal visibility (transparency) of the package.
Is not necessarily secured on the entire surface of the package. For example, when the pharmaceutical composition to be stored is an eye drop or an injection, the container (packaging body) of the container (packaging body) is used from the viewpoint of implementing the provisions of the general rules for eye drops in the Japanese Pharmacopoeia and the insoluble foreign matter inspection method for injections The transparent portion may occupy at least 80% or more, preferably 90% or more of the side surface area. The side surface of the container here means the side surface portion of the container, that is, the portion excluding the portion covered with the lid of the container and the portion corresponding to the bottom from the entire surface of the container. In addition, for example, at the distribution stage, the package used in the present invention has the internal visibility (transparency) of the package because a label for displaying a component or a product name is provided on the surface of the package. It does not prevent damage, but in the package, the portion having internal visibility (transparency) is secured to such an extent that the user can confirm the amount of the preparation inside the package. desirable.

In the present invention, blocking light having a wavelength of 350 to 450 nm means that the wavelength is 350 to 450.
Average light transmittance of nm (hereinafter referred to as average light transmittance in a wavelength region of 350 to 450 nm)
Means 20% or less. Here, as in the case of the average light transmittance in the visible light region of 455 to 780 nm, the light transmittance in the wavelength region of 350 to 450 nm is JIS K7150.
The average light transmittance in the wavelength region of 350 to 450 nm is measured, for example, every 350 nm between 350 and 450 nm, and each light transmission obtained is measured. It can obtain | require by calculating those average values from a rate.

From the viewpoint of more effectively suppressing the degradation of tranilast or a salt thereof by light, 3
A container having an average light transmittance in the wavelength region of 50 to 450 nm is preferably 15% or less, more preferably 10% or less, still more preferably 5% or less, and particularly preferably 3% or less.

In order to provide more excellent light stability to a pharmaceutical preparation containing tranilast or a salt thereof, one capable of blocking light having a wavelength of 350 to 430 nm is desirable. That is, the wavelength 350
A transparent package having an average transmittance (average transmittance) of light of ˜430 nm of 15% or less, preferably 10% or less, more preferably 5% or less, and further preferably 3% or less is more suitable. . Here, about the measuring method of the average transmittance | permeability of the light of wavelength 350-430 nm, 350-
This is the same as the method for measuring the average light transmittance in the wavelength region of 450 nm.

For example, the average of the transmittance of light having a wavelength of 365 to 430 nm (average transmittance) is 15%.
Hereinafter, if it is a transparent packaging body, which is preferably 10% or less, more preferably 5% or less, and even more preferably 3% or less, tranilast or a salt thereof can be provided with excellent light stability. In addition, about the measuring method of the average transmittance | permeability of light with a wavelength of 350-430 nm, 365-4
This is the same as the method for measuring the average light transmittance in the wavelength region of 30 nm.

Thus, the wavelength of 350 to 450 nm (preferably 350 to 430 nm,
It is possible to provide stability to the tranilast in the package by blocking the light of 365 to 430 nm and preventing the light in the wavelength region from being transmitted into the container.

As for the means for blocking light having a wavelength of 350 to 450 nm as described above, 455 to 780 is used.
Although there is no particular limitation as long as the average light transmittance in the visible light region of nm is ensured, for example, a method of kneading a substance that blocks light with a wavelength of 350 to 450 nm into the packaging material, the packaging body Method of applying a substance that blocks light having a wavelength of 350 to 450 nm, wavelength 350
A method of attaching a film kneaded with a substance blocking light of ˜450 nm to the package can be applied alone or in combination. As a method for mounting the film on a container, specifically, a heat shrinkable film (shrink film) that blocks light having a wavelength of 350 to 450 nm.
Can be exemplified by a method in which the film is put on the package and the film is heated to heat and cover the package.

The substance that blocks light having a wavelength of 350 to 450 nm is not particularly limited. For example, monoazo pigments such as Hansa pigments, benzimidazoline pigments, and pyrazolone pigments;
Disazo pigments such as diallylide pigments and pyrazolone pigments; condensed azo pigments such as yellow pigments; and condensed polycyclic pigments such as phthalocyanine pigments, perinone pigments, isoindolinone pigments and anthraquinone pigments be able to. These wavelengths 350-45
Substances that block 0 nm light may be used alone or in any combination of two or more. The substance may be used in combination with a pigment that does not itself block light having a wavelength of 350 to 450 nm.

When a substance that blocks light with a wavelength of 350 to 450 nm is kneaded into the packaging material, the compounding ratio of the substance in the packaging material varies depending on the type of the substance, the type of container material, etc. 0.001 to 15% by weight of the substance in the packaging material, preferably 0.00
The ratio which becomes 1 to 10 weight%, More preferably, it becomes 0.01 to 5 weight% can be mentioned.
With such a blending ratio, it becomes possible to block light of 350 to 450 nm.

As an embodiment of the transparent package (particularly in the form of a container) used in the present invention, for example, a yellow pigment (pigment yellow 183) and a yellow pigment (pigment yellow 110) may be used alone or in combination in the package material. A package body kneaded at a ratio of 0.001 to 5% by weight and formed into a container having a thickness of about 0.1 to 1 mm is exemplified.

The package used in the present invention is not limited with respect to the material (material), and may be any of glass, plastic, cellulose, pulp, rubber and the like. When the aqueous preparation is accommodated, a plastic container is preferable from the viewpoint of squeeze property and durability.

The resin of the plastic package used in the present invention is preferably a thermoplastic resin, such as an olefin resin (polyethylene, polypropylene, etc.), a polyester resin,
Polyphenylene ether resin, polycarbonate resin, polysulfone resin, polyamide resin, hard vinyl chloride resin, styrene resin (polystyrene, acrylonitrile-
Styrene copolymer (AS resin etc.) etc. can be illustrated. Preferred resins are polyethylene, polypropylene, polyester resins, and polycarbonate resins, and particularly preferred resins are polyester resins.

As the polyester resin, a resin composed of a dicarboxylic acid component (such as an aromatic dicarboxylic acid component such as phthalic acid, terephthalic acid, or naphthalenedicarboxylic acid) and a diol component can be used. Specifically, an aromatic polyester resin such as polyalkylene terephthalate [polyethylene terephthalate (PET), polybutylene terephthalate (P
Poly C _2-4 alkylene terephthalate such as BT), polyalkylene naphthalate [poly C _2-4 alkylene naphthalate such as polyethylene naphthalate (PEN), polybutylene naphthalate], polycycloalkylene terephthalate [poly ( 1,4-cyclohexylenedimethylene terephthalate (PCT), etc.], polyarylates (resins composed of bisphenols (bisphenol-A, etc.) and phthalic acids (phthalic acid, terephthalic acid), etc.) Is mentioned. The polyester resin also includes a copolyester containing the homopolyester unit as a main component (for example, 50% by weight or more), a copolymer of the homopolyester (such as a copolymer of PET and PCT), and the like. . Of these, olefin resins (such as polyethylene), aromatic polyester resins (polyethylene terephthalate, polyethylene naphthalate, polyarylate, etc.) and polycarbonate resins are preferred. The polycarbonate-based resin is, for example, an aromatic polycarbonate based on bisphenols (such as bisphenol-A).

In the present invention, the plastic package has strength, light transmittance, gas or water vapor barrier properties (
A polymer alloy (such as a polymer blend) may be used as long as it does not adversely affect moisture permeability. Preferred polymer alloys include polymer blends of a plurality of synthetic resins (such as polymer blends of PET and PEN). The resin is preferably a resin having good squeeze properties and durability against repeated pressing. In addition, by incorporating an ultraviolet absorber, an infrared absorber or the like into the resin, or by applying a coating agent containing the above components to the resin surface, the light stability of tranilast is further improved in cooperation with the effects of the present invention. May be improved.

As described above, the transparent package that blocks light having a wavelength of 350 to 450 nm can suppress the degradation of tranilast or a salt thereof by light. Therefore, the present invention is further characterized in that, from another point of view, the pharmaceutical preparation containing tranilast or a salt thereof is housed in a transparent package provided with a light shielding means for blocking light having a wavelength of 350 to 450 nm. A method for inhibiting photodegradation of tranilast or a salt thereof is provided.

In such a method, the type of tranilast or salt to be used and the content ratio in the pharmaceutical preparation, other components to be blended in the pharmaceutical preparation, the form of the pharmaceutical preparation, a transparent container that blocks light having a wavelength of 350 to 450 nm, etc. The same as in the case of the pharmaceutical preparation containing the transparent package.

The packaged pharmaceutical preparation of the present invention is obtained by containing a preparation containing tranilast in a container that ensures visibility, the preparation in the package can be observed with the naked eye, and the tranilast produced by exposure to light can be observed. Decomposition is remarkably suppressed. Therefore, according to the present invention, production process control and quality control of a preparation containing tranilast can be ensured, and the storage stability of the preparation containing tranilast can be enhanced.

In addition, according to the method for suppressing photodegradation of tranilast of the present invention, the degradation of tranilast by light is remarkably suppressed by a simple method of storing a pharmaceutical preparation containing tranilast in a transparent package that blocks a specific wavelength. can do. Therefore, according to the method, degradation of tranilast by light can be suppressed, and the amount, properties and insoluble foreign matter of the preparation in the package can be observed with the naked eye, facilitating quality control in manufacturing the preparation containing tranilast. Is done. In addition, the packaged preparation obtained by the method is advantageous in that the user of the preparation can use it after confirming the amount and properties of the preparation from the outside of the package with the naked eye.

It is a figure which shows the light transmittance of the red film used in Test Example 1. It is a figure which shows the light transmittance of the yellow film used in Test Example 1. It is a figure which shows the light transmittance of the green film used in Test Example 1. It is a figure which shows the light transmittance of the container (yellowish green) made from a polyethylene terephthalate used in Test Example 1. It is a figure which shows the light transmittance of the magenta film used in Test Example 1. It is a figure which shows the light transmittance of the glass-made transparent containers used in Test Example 1. It is a figure which shows the light transmittance of the container (transparent) made from a polypropylene used in Test Example 1. It is a figure which shows the light transmittance of the container (brown) made from the polypropylene used in Test Example 1. It is a figure which shows the light transmittance of the blue film used in Test Example 1. It is a figure which shows the light transmittance of the blue film laminated | stacked two sheets used in Test Example 1. FIG. FIG. 3 is a diagram showing light transmittance of three laminated blue films used in Test Example 1.

Hereinafter, the present invention will be described in detail based on examples, test examples, and the like, but the present invention is not limited thereto.
Test Example 1 Tranilast Decomposition Inhibition Confirmation Test A tranilast-containing preparation shown in Formulation Example 1 of Table 1 was prepared, and this was filtered through a 0.2 μm membrane filter. (Capacity 10 ml) and sealed. Using the thus obtained tranilast-containing preparations in various containers, a light stability tester (“Light-Tron LT-120 D3CJ type”, manufactured by Nagano Kagaku Co., Ltd.) and a D65 fluorescent lamp as a light source at room temperature 25 Each eye drop was exposed to light having a cumulative irradiation amount of 300,000 lux · hr by continuously irradiating light of 0.5000 lux at 60 ° C. for 60 hours. Thereafter, the tranilast concentration in each eye drop was analyzed by high performance liquid chromatography, and the residual concentration of tranilast was quantified. From the measured residual concentration of tranilast, the residual ratio (%) of tranilast relative to that before light irradiation was calculated. In addition, in order to evaluate the light transmittance of the container used in this test and the various films attached to the container, each container and the various films were cut into a flat shape, and this was used as a specimen to prepare a spectacle lens spectral transmittance meter TM- 1 (manufactured by Topcon Co., Ltd.) to measure light transmittance (see FIGS. 1 to 11), average light transmittance at 350 to 450 nm and 45
The average light transmittance at 5 to 780 nm was determined.

The container used for the test is a container made of glass, a container made of polypropylene (PP), and a container made of polyethylene terate (PET). These containers were equipped with various films as light-shielding means and those colored by kneading a brown or yellow-green pigment (see Table 2). The shrink film (heat-shrink film) was attached to the entire side surface of the container according to a conventional method, and the other films were attached by winding the film around the entire side surface of the container and fixing it with tape. In addition, the sources of the film used for the test are as follows: red film (Toyo Corporation, red cellophane), yellow film ((Toyo Corporation, yellow cellophane), green film (Toyo Corporation, green cellophane) ), Blue film (Toyo Corporation, blue cellophane), and reddish purple film (
Red-purple cellophane).

The internal visibility of the container used for the test was evaluated based on the following evaluation criteria.
<Evaluation criteria>
◎ The amount of internal formulation and foreign matter can be clearly seen ○ The amount of internal formulation and foreign matter can be visually recognized △ The amount of internal formulation can be seen, but no foreign matter can be seen × The amount of internal formulation cannot be seen

Among the containers used in the test, those having an average light transmittance of 455 to 780 nm of 30% or more,
The preparation contained inside was visible from the outside, and had sufficient transparency required for the container. Of the containers used in the test, the average light transmittance of 455 to 780 nm is 30% or more in a container equipped with red, yellow and green films, and a container made of yellow-green PET, and 350 to 450 nm. It was confirmed that the light can be effectively blocked (see FIGS. 1 to 4 and Table 2).

The results of the residual ratio of tranilast after light irradiation are also shown in Table 2. As is clear from Table 2, the tranilast-containing preparation contained in a container where light of 350 to 450 nm (particularly 350 to 430 nm) was blocked showed a significantly high value of the residual tranilast after light irradiation.
Although not shown in Table 2, it was confirmed that tranilast was more stably held in the container as the transmittance of light in the wavelength region of 365 to 430 nm was lower, even within the range of 350 to 450 nm. On the other hand, it was confirmed that the tranilast-containing preparation contained in a container having a high light transmittance of 350 to 450 nm cannot suppress the degradation of tranilast by light irradiation.

From the above results, it becomes clear that light of 350 to 450 nm is involved in the degradation of tranilast due to light exposure, and by blocking light in such a wavelength region, degradation due to light exposure of tranilast can be suppressed, 455 of the container containing the tranilast-containing preparation
It was confirmed that if the average light transmittance at 780 nm was 30% or more, good internal visibility could be secured.

Example 7-11 Eyedrops in a container Each component described in Formulation Example 2-6 in Table 3 was weighed and dissolved in an appropriate amount of purified water to adjust the pH to 7.5, and the total amount was 100 ml with purified water ( Osmotic pressure ratio to physiological saline = 1
. 0), and then sterilized by filtration in an aseptic environment, filled in a “PP transparent container equipped with a yellow shrink film” used in Test Example 1, and filled with eye drops (Examples 7 to 7).
11) was prepared. About the obtained eye drop in a container (Example 7-11), when exposed to light having an integrated irradiation amount of 300,000 lux · hr by the same method as in Test Example 1,
The tranilast residual rate was 80% or more in any of the eye drops in containers.

Examples 12-16 Eye Drops in Containers As a container for eye drops, a yellow pigment (pigment yellow 183) and a yellow pigment (pigment yellow)
110) were each prepared at a thickness of 0.4 mm of a polypropylene resin containing 0.1% by weight. The container had transparency (internal visibility) to such an extent that the amount of the internal preparation and foreign matters could be clearly visually recognized from the outside. Each component described in Formulation Example 2-6 in Table 3 is weighed and dissolved in an appropriate amount of purified water to adjust the pH to 7.5, and the total amount is 100 ml with purified water (osmotic pressure ratio to physiological saline = 1. After 0), the solution was sterilized by filtration in an aseptic environment, and these were filled in the container to prepare eye drops in containers (Examples 12 to 16). For the obtained eye drop in a container (Examples 12-16), the cumulative irradiation amount was 300,000 lux · hr by the same method as in Test Example 1 above.
As a result, the tranilast residual rate was 80% or more in any ophthalmic solution.

Claims (1)

A pharmaceutical preparation containing a transparent package, wherein the pharmaceutical preparation containing tranilast or a salt thereof is placed in a transparent package having an average light transmittance of 20% or less in a wavelength region of 350 to 450 nm.

Images