Pharmaceutical preparations

Abstract

This invention provides a technique for inhibiting the decomposition of loxoprofen contained in a composition. A pharmaceutical preparation comprises: a pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates; and a packaging body encapsulating the pharmaceutical composition; and has at least one of the following configurations: Option 1, the average transmittance of the packaging body in the wavelength region of 550–600 nm is 55.0% or less; Option 2, the maximum transmittance of the packaging body in the wavelength region of 550–600 nm is 57.0% or less.

Description

Technical Field

[0001] This invention relates to pharmaceutical preparations. Background Technology

[0002] As a technique for improving the storage stability of pharmaceutical compositions, there are techniques described in Patent Documents 1 to 3.

[0003] Patent document 1 (International Publication No. 01 / 068061) describes a patch having a support body that has undergone ultraviolet shielding treatment (claim 1). By performing ultraviolet shielding treatment on the support body of the patch, which is composed of a single layer, the skin at the application site is protected from ultraviolet radiation. In addition, if the base of the patch contains a drug, the drug decomposition caused by ultraviolet radiation can be significantly inhibited (page 5, lines 2-5).

[0004] Patent document 2 (Japanese Patent Application Publication No. 2023-86793) discloses an ophthalmic pharmaceutical product comprising an eye drop contained in a transparent container. The eye drop contains brimonidine and / or its salt, and brinzolamide and / or its salt. The transparent container has a maximum transmittance of 67% or less for light with a wavelength of 360 to 460 nm and a maximum transmittance of 78% or less for light with a wavelength of 600 to 680 nm (claim 1). Thus, the eye drop containing brimonidine and / or its salt, as well as brinzolamide and / or its salt, can achieve photostability of brimonidine and / or its salt, exhibiting excellent formulation stability. Furthermore, since the eye drop is contained in a transparent package in which the interior can be seen, insoluble foreign matter tests can be easily performed, making quality control easier. Moreover, since the remaining amount of eye drop can be seen from the outside of the container, user convenience is also improved (paragraph 0012).

[0005] Furthermore, Patent Document 3 (Japanese Patent Application Publication No. 7-118147) discloses a vitamin A-soluble aqueous eye drop that, by incorporating vitamin A, a nonionic surfactant at 250-1000% by weight relative to vitamin A, and menthol or its analogues at 5-50% by weight relative to vitamin A, improves the characteristic odor of vitamin A and has excellent usability; by incorporating one or more components from at least one of the following groups: flavin adenine dinucleotide or its salt, chondroitin sulfate or its salt, and glycyrrhizic acid or its salt, it prevents the accelerated decomposition of vitamin A over time caused by flavin adenine dinucleotide or its salt; and by filling it into a container made of acrylonitrile resin with pigments that shield wavelengths below 380 nm, it remains stable against oxygen and light even after long-term storage in the container, and the internal solution does not adsorb or migrate into the container, thus exhibiting stable properties (paragraph 0018).

[0006] Existing technical documents

[0007] Patent documents

[0008] Patent Document 1: International Publication No. 01 / 068061

[0009] Patent Document 2: Japanese Patent Application Publication No. 2023-86793

[0010] Patent Document 3: Japanese Patent Application Publication No. 7-118147 Summary of the Invention

[0011] According to the inventors' research, it has been learned that in compositions containing loxoprofen, the loxoprofen may sometimes decompose during storage.

[0012] Therefore, the present invention provides a technique for inhibiting the decomposition of loxoprofen contained in a composition.

[0013] The present invention is described below.

[0014] [1] A pharmaceutical preparation comprising:

[0015] A pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates, and

[0016] Packaging material covering the above-mentioned pharmaceutical composition;

[0017] The average transmittance of the above-mentioned packaging in the wavelength region of 550-600nm is less than 55.0%.

[0018] [2] According to the pharmaceutical preparation described in [1], the maximum transmittance of the above-mentioned packaging body in the wavelength region of 550 to 600 nm is less than 57.0%.

[0019] [3] A pharmaceutical preparation comprising:

[0020] A pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates, and

[0021] Packaging material covering the above-mentioned pharmaceutical composition;

[0022] The maximum transmittance of the above-mentioned packaging in the wavelength region of 550-600nm is less than 57.0%.

[0023] [4] The pharmaceutical preparation according to any one of [1] to [3], wherein the interior of the above-mentioned packaging body can be seen.

[0024] [5] The pharmaceutical preparation according to any one of [1] to [4], wherein the average transmittance of the packaging body in the wavelength region of 600 to 700 nm is 57.0% or less.

[0025] [6] The pharmaceutical preparation according to any one of [1] to [5], wherein the maximum transmittance of the packaging body in the wavelength region of 600 to 700 nm is 59.0% or less.

[0026] [7] The pharmaceutical preparation according to any one of [1] to [6], wherein the ratio R(500 / 550) of the transmittance of the above-mentioned packaging body at a wavelength of 500 nm to the transmittance at a wavelength of 550 nm is 0.5 to 3.

[0027] [8] The pharmaceutical preparation according to any one of [1] to [7], wherein the packaging body shields ultraviolet light in the wavelength region below 400 nm.

[0028] [9] The pharmaceutical preparation according to any one of [1] to [8], wherein the material of the packaging body comprises at least one selected from resin materials and metal materials.

[0029]

[10] The pharmaceutical preparation according to any one of [1] to [9], wherein the packaging body is made of polyolefin resin, polyester resin or aluminum.

[0030]

[11] The pharmaceutical preparation according to any one of [1] to

[10] , wherein the packaging body is a container.

[0031]

[12] The pharmaceutical preparation according to any one of [1] to

[10] , wherein the packaging body is a film.

[0032]

[13] The pharmaceutical preparation according to any one of [1] to [9], wherein the packaging body is PTP.

[0033]

[14] A pharmaceutical preparation according to any one of [1] to

[13] , wherein the pharmaceutical composition is an external application.

[0034]

[15] The pharmaceutical preparation according to

[14] , wherein the above-mentioned topical agent is selected from any one of liquid, gel, cream, spray, aerosol, ointment and hard gel.

[0035]

[16] The pharmaceutical preparation according to

[14] or

[15] , wherein the above-mentioned topical preparation is a liquid.

[0036]

[17] The pharmaceutical preparation according to

[16] , wherein the liquid preparation comprises at least one selected from water, aliphatic alcohols having 1 to 4 carbon atoms, and polyols.

[0037]

[18] The pharmaceutical preparation according to any one of

[14] to

[17] , wherein, relative to the total pharmaceutical composition, the content of the above-mentioned loxoprofen, its salt and their hydrates in the pharmaceutical composition is 0.1% to 10% by mass in anhydrous form.

[0038]

[19] A pharmaceutical preparation according to any one of [1] to

[18] , wherein the pharmaceutical composition further comprises 1-menthol.

[0039] It should be noted that any combination of these components, as well as variations in the expression of the present invention among methods, apparatuses, etc., are all valid ways of presenting the present invention.

[0040] For example, according to the present invention, a method for inhibiting the decomposition of at least one selected from loxoprofen, its salts, and their hydrates in a pharmaceutical preparation may also be provided, comprising the following steps:

[0041] A process for preparing a pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates; and

[0042] The process of obtaining a pharmaceutical preparation by encapsulating the above-mentioned pharmaceutical composition in a packaging body with an average transmittance of less than 55.0% in the wavelength region of 550 to 600 nm.

[0043] Additionally, according to the present invention, for example, a method for inhibiting the decomposition of at least one selected from loxoprofen, its salts, and their hydrates in a pharmaceutical preparation may also be provided, comprising the following steps:

[0044] A process for preparing a pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates; and

[0045] The process of obtaining a pharmaceutical preparation by encapsulating the above-mentioned pharmaceutical composition in a packaging body with a maximum transmittance of less than 57.0% in the wavelength region of 550 to 600 nm.

[0046] According to the present invention, the decomposition of loxoprofen contained in the composition can be suppressed. Detailed Implementation

[0047] The embodiments of the present invention will be described below. In this embodiment, each component may be included in the composition alone or in combination of two or more. Each component may be a commercially available product, or may be manufactured and used by known methods. Furthermore, the salt of the compound may be, for example, a pharmaceutically or physiologically acceptable salt.

[0048] In this specification, the "~" sign indicating a numerical range means above or below, with both values ​​at either end included.

[0049] (Pharmaceutical preparations)

[0050] In this embodiment, the pharmaceutical preparation comprises: a pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates (hereinafter also referred to as "loxoprofen class"), and a packaging body encapsulating the pharmaceutical composition. Regarding the optical properties of the packaging body, the pharmaceutical preparation has at least one of the configurations described in embodiments 1 and 2 below.

[0051] (Method 1) The average transmittance of the packaging in the wavelength region of 550–600 nm is below 55.0%.

[0052] (Method 2) The maximum transmittance of the packaging in the wavelength region of 550-600nm is less than 57.0%.

[0053] The inventors have discovered that by controlling the optical properties of the packaging in a specific wavelength range of 550–600 nm, the decomposition of loxoprofen contained in the pharmaceutical composition contained within the packaging can be effectively suppressed.

[0054] In this embodiment, since the pharmaceutical composition containing loxoprofen is encapsulated by a packaging body having at least one of the configurations of methods 1 and 2, the decomposition of loxoprofen contained in the pharmaceutical composition can be appropriately suppressed. Furthermore, for example, the storage stability of the pharmaceutical composition can be improved. The decomposition of loxoprofen is, for example, photodecomposition, and more specifically, decomposition that occurs due to light irradiation or light exposure of the pharmaceutical preparation.

[0055] Furthermore, according to this embodiment, for example, it is also possible to appropriately suppress the time-dependent decomposition of loxoprofen and the resulting generation of unknown decomposition products.

[0056] (Packaging)

[0057] In this embodiment, the packaging body has at least one of the configurations 1 and 2, and preferably both configurations 1 and 2. This allows for more reliable suppression of the decomposition of loxoprofen-like compounds in the pharmaceutical composition.

[0058] From the same perspective, the packaging body has at least one of the following configurations in a portion or in whole the area covering the pharmaceutical composition, preferably having at least one of the following configurations in whole.

[0059] In Method 1, the average transmittance of the packaging in the wavelength region of 550–600 nm is, for example, 55.0% or less, preferably 30% or less, more preferably 20% or less, and even more preferably 10% or less. This allows for more reliable suppression of the decomposition of loxoprofen-like substances in the pharmaceutical composition.

[0060] In addition, the average transmittance of the packaging in the wavelength region of 550-600nm is specifically above 0%, for example, it can be above 1% or above 5%.

[0061] In Method 2, the maximum transmittance of the packaging in the wavelength region of 550–600 nm is, for example, 57.0% or less, preferably 40% or less, more preferably 30% or less, even more preferably 20% or less, and even more preferably 10% or less. This allows for more reliable suppression of the decomposition of loxoprofen-like compounds in the pharmaceutical composition.

[0062] In addition, the maximum transmittance of the packaging in the wavelength region of 550-600nm is specifically above 0%, for example, it can be above 1% or above 5%.

[0063] In addition, the packaging should preferably allow visibility of the interior. This allows for easy monitoring of the remaining amount of the pharmaceutical composition while inhibiting the decomposition of loxoprofen-like substances within the composition.

[0064] In this case, the packaging body can be configured such that at least a portion of the surface covering the pharmaceutical composition allows the interior to be seen. For example, the packaging body can be provided with a window having at least one of methods 1 and 2, and the interior can be seen through the window. The shape of the window can be, for example, slit-shaped, strip-shaped, circular, or polygonal.

[0065] The average transmittance of the packaging body in the wavelength region of 450-500nm is specifically 0% or more, for example, 1% or more or 5% or more, and for example, 45% or less, preferably 30% or less, and more preferably 10% or less.

[0066] In addition, the maximum transmittance of the packaging body in the wavelength region of 450-500nm is specifically 0% or more, for example, 1% or more or 5% or more, and for example, 45% or less, preferably 20% or less, and more preferably 10% or less.

[0067] The average transmittance of the packaging body in the wavelength region of 500-550nm is specifically 0% or more, for example, 1% or more or 5% or more, and for example, 43% or less, preferably 30% or less, and more preferably 10% or less.

[0068] In addition, the maximum transmittance of the packaging body in the wavelength region of 500-550nm is specifically 0% or more, for example, 1% or more or 5% or more, and for example, 50% or less, preferably 30% or less, and more preferably 10% or less.

[0069] The average transmittance of the packaging in the wavelength region of 600-700 nm is, for example, 57.0% or less, preferably 55.0% or less, more preferably 30% or less, even more preferably 20% or less, and even more preferably 10% or less. This allows for more reliable suppression of the decomposition of loxoprofen-like substances in the pharmaceutical composition.

[0070] In addition, the average transmittance of the packaging in the wavelength region of 600-700nm is specifically above 0%, for example, it can be above 1% or above 5%.

[0071] The maximum transmittance of the packaging in the wavelength region of 450–500 nm is, for example, 45% or less, preferably 35% or less, more preferably 25% or less, even more preferably 20% or less, and even more preferably 10% or less. This allows for more reliable suppression of the decomposition of loxoprofen-like compounds in the pharmaceutical composition.

[0072] In addition, the maximum transmittance of the packaging in the wavelength region of 450-500nm is specifically above 0%, for example, it can be above 1% or above 5%.

[0073] The maximum transmittance of the packaging in the wavelength region of 500–550 nm is, for example, 45% or less, preferably 30% or less, more preferably 20% or less, even more preferably 10% or less, and even more preferably 5% or less. This allows for more reliable suppression of the decomposition of loxoprofen-like compounds in the pharmaceutical composition.

[0074] In addition, the maximum transmittance of the packaging in the wavelength region of 500-550nm is specifically above 0%, for example, it can be above 1% or above 5%.

[0075] The maximum transmittance of the packaging in the wavelength region of 600–700 nm is, for example, 59.0% or less, preferably 57.0% or less, more preferably 30% or less, even more preferably 20% or less, and even more preferably 10% or less. This allows for more reliable suppression of the decomposition of loxoprofen-like compounds in the pharmaceutical composition.

[0076] In addition, the maximum transmittance of the packaging in the wavelength region of 600-700nm is specifically above 0%, for example, it can be above 1% or above 5%.

[0077] Specifically, the average and maximum transmittance of the packaging can be determined as follows: using a spectrophotometer (e.g., Shimadzu UV-2700 UV-Vis spectrophotometer), with air as a control, the transmittance of the packaging to light with wavelengths of 300–800 nm is measured at 0.5 nm intervals, and the average and maximum transmittance are calculated respectively.

[0078] In addition, the packaging body preferably has the following optical properties. These can be measured, for example, according to the methods described above for measuring average transmittance and maximum transmittance.

[0079] The ratio R(500 / 550) of the transmittance of the packaging at a wavelength of 500 nm to that at a wavelength of 550 nm is preferably 0.5 or more, more preferably 0.8 or more, even more preferably 1.0 or more, and preferably 3 or less, more preferably 2.8 or less, even more preferably 2.6 or less. This allows for more reliable suppression of the decomposition of loxoprofen-like substances in the pharmaceutical composition.

[0080] The packaging material preferably shields against ultraviolet light in the wavelength range below 400 nm. This allows for more reliable inhibition of the decomposition of loxoprofen-like substances in pharmaceutical compositions.

[0081] The ultraviolet radiation in the wavelength region below 400nm specifically refers to at least one or a portion of ultraviolet A (UV-A: 315~400nm), ultraviolet B (UV-B: 280~315nm), and ultraviolet C (UV-C: 200~280nm), preferably the entire UV-A to UV-C region.

[0082] The shielding can be complete or partial, with complete shielding being preferred. More specifically, the maximum transmittance of ultraviolet light in the wavelength region below 400 nm of the packaging body is preferably less than 10%, more preferably less than 5%, and even more preferably less than 1%.

[0083] The transmittance of the packaging at a wavelength of 600 nm is preferably 50% or less, more preferably 20% or less, even more preferably 15% or less, and even more preferably 10% or less. This allows for more reliable suppression of the decomposition of loxoprofen-like compounds in the pharmaceutical composition.

[0084] In addition, the transmittance of the packaging at a wavelength of 600nm is specifically above 0%, for example, it can be above 1% or above 5%.

[0085] The type and material of the packaging can be selected based on the ingredients contained in the pharmaceutical composition contained within the packaging and the dosage form of the pharmaceutical composition.

[0086] The packaging body can be, for example, a container selected from bottles (glass bottles, etc.), cans, resin bottles (made of synthetic resin, natural resin, etc.), boxes (e.g., individual packaging boxes); and at least one other packaging style such as film, PTP (Press Through Package), SP (Strip Package), bag packaging, strip packaging containers, pillow packaging, etc., preferably a container, film, or PTP. This allows for more stable suppression of the decomposition of loxoprofen. From the same perspective, a combination of multiple packaging styles is preferred, such as a laminate of containers (bottles, etc.) and films.

[0087] Furthermore, the packaging material is preferably a container capable of airtight packaging. This allows for a more appropriate improvement in the storage stability of the pharmaceutical composition.

[0088] The packaging material comprises one or more materials selected from inorganic materials (such as glass), resin materials, metal materials, and paper materials, preferably at least one material selected from resin materials and metal materials. This allows for more stable inhibition of the decomposition of loxoprofen-like substances.

[0089] Examples of resin materials include thermoplastic resins, and more specifically, polyolefins such as polyethylene (high-density polyethylene, low-density polyethylene, etc.), polypropylene, polyesters such as polyethylene terephthalate, polystyrene, and biomass polyethylene, which are resins derived from plants.

[0090] In addition, aluminum is an example of a metallic material.

[0091] From the perspective of more stably inhibiting the decomposition of loxoprofen, the packaging body is preferably made of polyolefin resin, polyester resin, or aluminum.

[0092] In addition, materials used in films, SPs, PTPs, strip packaging, pillow packaging, etc., include, for example, resin films such as polypropylene films, polyethylene terephthalate films, and polyethylene films, or materials with aluminum foil attached to these resin films. Either single-layer films or multi-layer films (e.g., laminated films) can be used.

[0093] Furthermore, the packaging material preferably includes materials that are not easily affected by moisture. Examples of such containers include packaging containers formed from at least one of moisture-proof materials and gas-barrier materials.

[0094] As a moisture-proof material, examples include a combination of PTP (polypropylene) and polyethylene aluminum pillows. As a combined material, examples include PTP packaging (Al-Al packaging) using aluminum on both sides.

[0095] Gas barrier materials can be, for example, laminated films with functional barrier layers, which can also function as the aforementioned moisture-proof materials, or can be used together with the aforementioned moisture-proof materials.

[0096] In addition, at least a portion of the packaging can be made environmentally friendly. For example, environmentally friendly materials such as recycled plastics, biomass plastics, and biodegradable plastics can be used in part or all of the packaging.

[0097] The thickness of the packaging body can be, for example, 10 μm or more, preferably 20 μm or more, and also 100 μm or more. This allows for increased packaging strength while inhibiting the decomposition of loxoprofen.

[0098] In addition, the thickness of the packaging is preferably 10 mm or less, more preferably 5 mm or less. This allows the pharmaceutical preparation to be made thinner and smaller overall.

[0099] In addition, when the packaging includes a film, the thickness of the film is, for example, 1 μm or more, preferably 5 μm or more, and for example, 200 μm or less, preferably 100 μm or less.

[0100] Next, the pharmaceutical composition will be described.

[0101] (Pharmaceutical Composition)

[0102] The pharmaceutical composition contains at least one of the following: loxoprofen, its salts, and their hydrates. Specifically, loxoprofen and its salts can be hydrates (hydrated salts).

[0103] Specific examples of salts include monovalent metal salts such as sodium and potassium.

[0104] Loxoprofen compounds are preferably selected from one or more compounds chosen from loxoprofen, loxoprofen sodium, loxoprofen sodium monohydrate, and loxoprofen sodium dihydrate, with loxoprofen sodium dihydrate being more preferred. Loxoprofen sodium dihydrate is listed in the 18th revised edition of the Japanese Pharmacopoeia in the form of loxoprofen sodium hydrate.

[0105] In the case of a topical formulation, the content of loxoprofen in the pharmaceutical composition, calculated on an anhydrous basis, is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and even more preferably 1% by mass or more, relative to the overall pharmaceutical composition. This allows for efficient and appropriate therapeutic effects. Furthermore, in the case of a solid formulation, the content of loxoprofen in the pharmaceutical composition, calculated on an anhydrous basis, can be, for example, 5% by mass or more, 10% by mass or more, 15% by mass or more, or 20% by mass or more.

[0106] In the case of a topical formulation, the content of loxoprofen in the pharmaceutical composition, calculated on an anhydrous basis, is preferably 10% by mass or less, more preferably 7% by mass or less, even more preferably 5% by mass or less, even more preferably 3% by mass or less, and even more preferably 2% by mass or less. This allows for more stable inhibition of loxoprofen deterioration. Furthermore, in the case of a solid formulation, the content of loxoprofen in the pharmaceutical composition, calculated on an anhydrous basis, can be, for example, 40% by mass or less, 35% by mass or less, 30% by mass or less, or 25% by mass or less.

[0107] When the pharmaceutical composition is a solid composition, the content of loxoprofen in the solid composition, calculated on a daily basis and converted to anhydrous form, is preferably 10-540 mg, more preferably 30-360 mg, and even more preferably 30-270 mg.

[0108] The following examples of topical formulations and solid formulations are provided as illustrations of pharmaceutical compositions.

[0109] <Regarding the topical formulation>

[0110] As one embodiment of this invention, the following primarily illustrates the case where the pharmaceutical composition is a topical formulation. The components included in the topical formulation may be selected, for example, according to the dosage form of the topical agent described later.

[0111] Pharmaceutical compositions may contain ingredients other than loxoprofen.

[0112] For example, pharmaceutical compositions may further contain an aqueous base.

[0113] The aqueous base is, for example, at least one selected from water and aliphatic alcohols having 1 to 4 carbon atoms.

[0114] The water content in a pharmaceutical composition can be, for example, the amount remaining after removing all components other than water from the pharmaceutical composition.

[0115] Furthermore, from the perspective of making the water-soluble base agent easy to dissolve, in the case of a topical formulation, the water content in the pharmaceutical composition is preferably 20% by mass or more, more preferably 30% by mass or more, and even more preferably 35% by mass or more. In addition, it can be 37% by mass or more, 42% by mass or more, 47% by mass or more, or 52% by mass or more.

[0116] Furthermore, in the case of a topical formulation, the water content in the pharmaceutical composition, relative to the overall pharmaceutical composition, is, for example, 99% by mass or less, preferably 70% by mass or less, more preferably 60% by mass or less, and even more preferably 50% by mass or less. This increases the flexibility in the formulation of the aqueous base. Additionally, the water content in the pharmaceutical composition, relative to the overall pharmaceutical composition, can be 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, or 20% by mass or less. Furthermore, an anhydrous composition can also be formulated depending on the dosage form of the pharmaceutical composition, etc.

[0117] Aliphatic alcohols having 1 to 4 carbon atoms are, for example, one or more components selected from methanol, ethanol, propanol, isopropanol and butanol, with ethanol being preferred.

[0118] Ethanol is listed in the 2021 Dictionary of Pharmaceutical Additives (Pharmaceutical Daily News, 2021) and can be used in external preparations, for example, as a solubilizer, base, preservative, solvent, and cosolvent. Ethanol with a content of 99.5% by volume or more is also called anhydrous ethanol, but the ethanol in this embodiment also includes anhydrous ethanol.

[0119] The ethanol content in the pharmaceutical composition, relative to the overall pharmaceutical composition, is preferably 10% by mass or more, more preferably 20% by mass or more, even more preferably 30% by mass or more, even more preferably 40% by mass or more, and even more preferably 42.5% by mass or more. This allows the pharmaceutical composition to dry easily after application to the skin or other application sites. Furthermore, the ethanol content in the pharmaceutical composition, relative to the overall pharmaceutical composition, can be 1% by mass or more, 5% by mass or more, or 7% by mass or more.

[0120] Furthermore, relative to the overall pharmaceutical composition, the ethanol content in the pharmaceutical composition is preferably 75% by mass or less, more preferably 70% by mass or less, even more preferably 60% by mass or less, even more preferably 55% by mass or less, even more preferably 50% by mass or less, and even more preferably 47.5% by mass or less. This reduces irritation to the skin and other application sites. Additionally, relative to the overall pharmaceutical composition, the ethanol content in the pharmaceutical composition can be 40% by mass or less, 35% by mass or less, 25% by mass or less, 20% by mass or less, or 13% by mass or less.

[0121] (l-menthol)

[0122] In addition, pharmaceutical compositions may further contain l-menthol. l-menthol is listed in the 18th revised edition of the Japanese Pharmacopoeia or the Dictionary of Pharmaceutical Additives 2021.

[0123] The content of l-menthol in the pharmaceutical composition, relative to the overall pharmaceutical composition, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.5% by mass or more, even more preferably 1% by mass or more, and even more preferably 2% by mass or more. This allows users of the pharmaceutical preparation to experience a greater cooling sensation and analgesic effect, for example. Furthermore, the content of l-menthol in the pharmaceutical composition, relative to the overall pharmaceutical composition, can be 2.5% by mass or more, 3.5% by mass or more, or 5% by mass or more.

[0124] Furthermore, the content of l-menthol in the pharmaceutical composition is preferably 20% by mass or less, more preferably 15% by mass or less, even more preferably 10% by mass or less, and even more preferably 6% by mass or less, relative to the overall pharmaceutical composition. This reduces irritation to the skin and other application sites. Additionally, the content of l-menthol in the pharmaceutical composition can be 9% by mass or less, 8% by mass or less, 7% by mass or less, 5.5% by mass or less, or 4% by mass or less, relative to the overall pharmaceutical composition.

[0125] In addition, drugs or pharmaceutical additives other than the above-mentioned ingredients can be added to the pharmaceutical composition. For example, ingredients commonly used in topical skin preparations for analgesia and anti-inflammation can be added.

[0126] The aforementioned drugs are, for example, anti-inflammatory agents selected from glycyrrhizic acid and its salts, glycyrrhetinic acid, tranexamic acid, etc.; antihistamines such as diphenhydramine or its salts, diphenylimidazole, chlorpheniramine maleate, etc.; components that improve blood circulation such as tocopheryl acetate, benzyl nicotinate, etc.; terpenes containing dl-camphor, d-camphor, nonanoic acid vanillylamide, menthol, thymol, borneol, etc.; essential oils containing terpenes such as turpentine oil, peppermint oil, eucalyptus oil, etc.; local irritants such as capsicum extract, capsicum tincture, capsaicin, vanilloids, etc.; medicinal ingredients such as arnica tincture, belladonna extract, licorice, horse chestnut seeds or extracts, etc.; bactericidal ingredients such as isopropyl methylphenol; and astringent and anti-inflammatory agents such as zinc oxide, etc., and these drugs may be combined with the present invention within the scope of not impairing the effects of the present invention.

[0127] When a pharmaceutical composition contains tocopherol acetate, the content of tocopherol acetate in the pharmaceutical composition is, for example, 0.1 to 4% by mass relative to the total pharmaceutical composition.

[0128] In addition, when the pharmaceutical composition contains vanillinamide nonanoate, the content of vanillinamide nonanoate in the pharmaceutical composition is, for example, 0.001 to 0.05 by mass relative to the whole pharmaceutical composition.

[0129] In addition, as pharmaceutical additives, examples include substances added as needed to achieve long-term stability of content or to further improve user experience. Specific examples of pharmaceutical additives include base agents, thickeners, solubilizers, humectants, moisturizers, binders, pH adjusters, antioxidants, cooling agents, surfactants, stabilizers, emulsifiers, curing agents, colorants, fillers, crosslinking agents, gelling agents, and thickeners.

[0130] The base agent is, for example, one or more of the following polyols selected from styrene-isoprene-styrene copolymer, polyisobutylene, liquid paraffin, octyldodecyl alcohol, partially neutralized polyacrylic acid, polyvinyl alcohol (partially saponified), propylene glycol, dipropylene glycol, polyethylene glycol (e.g., polyethylene glycol 400), 1,3-butanediol, glycerol, D-sorbitol, hydrogenated rosin glycerol ester, etc., preferably containing polyols, more preferably containing at least one selected from 1,3-butanediol and glycerol.

[0131] Relative to the overall pharmaceutical composition, the content of the base agent in the pharmaceutical composition is, for example, 0.5% by mass or more, preferably 1% by mass or more, more preferably 2% by mass or more, further preferably 3% by mass or more, and even more preferably 15% by mass or more. Alternatively, it can be, for example, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, or 30% by mass or less, preferably 20% by mass or less, more preferably 15% by mass or less, further preferably 10% by mass or less, and even more preferably 8% by mass or less. Alternatively, it can be, for example, 6% by mass or less, 4.5% by mass or less, 3.5% by mass or less, 2.5% by mass or less, or 1.5% by mass or less. This results in a good skin-friendly feel after coating.

[0132] Furthermore, when the pharmaceutical composition is anhydrous or the water content is 5% by mass or less relative to the total pharmaceutical composition, the content of the base agent in the pharmaceutical composition can be the remaining amount after removing other components from the pharmaceutical composition. In this case, the content of the base agent in the pharmaceutical composition relative to the total pharmaceutical composition is, for example, 35% by mass or more, preferably 40% by mass or more, more preferably 45% by mass or more, even more preferably 50% by mass or more, and for example, 70% by mass or less, preferably 65% ​​by mass or less, more preferably 60% by mass or less, even more preferably 55% by mass or less, or it can be 50% by mass or less, 45% by mass or less, or 40% by mass or less.

[0133] Thickeners may be, for example, cellulose derivatives selected from hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl methyl cellulose, methyl cellulose, ethyl cellulose, etc.; other polysaccharides such as xanthan gum, pectin, guar gum, locust bean gum, carrageenan, sodium alginate, propylene glycol alginate, etc.; peptides such as gelatin; polyols such as polyethylene glycol (e.g., polyethylene glycol 20000), glycerin, etc.; and one or more water-soluble polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, etc., preferably including cellulose derivatives, more preferably including hydroxypropyl methyl cellulose.

[0134] The methoxy content in hydroxypropyl methylcellulose is, for example, about 27.0% to 30.0%, preferably about 28.0% to 30.0%.

[0135] In addition, the amount of hydroxypropoxy groups in hydroxypropyl methylcellulose is, for example, about 4.0 to 12.0%, preferably about 7.0 to 12.0%.

[0136] The content of thickener in the pharmaceutical composition, relative to the overall pharmaceutical composition, is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, even more preferably 0.1% by mass or more, even more preferably 0.2% by mass or more, and preferably 5% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less. This allows for the adjustment to a suitable viscosity that is easy to coat and does not drip easily.

[0137] In addition, the content of thickener in the pharmaceutical composition may be, for example, less than 10% by mass, relative to the overall pharmaceutical composition.

[0138] The solvent is, for example, one or more of the following: benzyl alcohol, pyrothiodecane, clomiphene, isopropyl myristate, polyethylene glycol (PEG), polybutylene glycol and other polyalkylene glycols; polyethylene glycol monostearate and other alkylene fatty acid esters; diisopropyl adipate; polyoxyethylene hydrogenated castor oil; and polysorbate.

[0139] The content of the solvent in the pharmaceutical composition is, for example, 0.1 to 5% by mass relative to the total pharmaceutical composition.

[0140] The wetting agent is, for example, at least one selected from hyaluronic acid, dl-pyrrolidone carboxylic acid and its salts (e.g., sodium dl-pyrrolidone carboxylic acid) and polysorbate 40 solution.

[0141] Moisturizers include, for example, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, liquid paraffin, glycerin, polyethylene glycol, 1,3-propanediol, 1,4-butanediol, and other polyols.

[0142] Adhesives, for example, are selected from the following: octyl acrylate copolymer, vinyl acrylate copolymer, 2-ethylhexyl acrylate-vinylpyrrolidone copolymer solution, 2-ethylhexyl acrylate-2-ethylhexyl methacrylate-dodecyl methacrylate copolymer solution, ethyl acrylate-methyl methacrylate copolymer dispersion, methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, acrylic resin alkanolamine solution, methacrylic acid-n-butyl acrylate copolymer, acrylic silk fibroin copolymer resin, and acrylic grafted starch (e.g., acrylic grafted starch 300, acrylic grafted starch 1). 000), butyl acrylate·2-ethylhexyl methacrylate·diacetone acrylamide copolymer, butyl acrylate·2-hydroxyethyl methacrylate·diacetone acrylamide copolymer, butyl acrylate·ethyl acrylate·2-hydroxyethyl methacrylate·diacetone acrylamide copolymer, butyl acrylate·2-ethylhexyl acrylate·2-hydroxyethyl methacrylate·diacetone acrylamide copolymer, isononyl acrylate·2-hydroxyethyl methacrylate·diacetone acrylamide copolymer, 2-ethylhexyl acrylate·2-hydroxyethyl methacrylate·diacetone acrylamide copolymer, butyl acrylate·2-ethylhexyl ...·diacetone acrylamide·diacetone acrylamide·diacetone acrylamide·diacetone acrylamide·diacetone acrylamide·di Acrylic adhesives such as ester-3-hydroxypropyl methacrylate-2-hydroxyethyl methacrylate-diacetone acrylamide copolymer, butyl acrylate-ethyl acrylate-3-hydroxypropyl methacrylate-diacetone acrylamide copolymer, etc.; cis-isoprene rubber, styrene-isoprene rubber, cis-polyisoprene rubber, high-cis-polyisoprene rubber, styrene-butadiene rubber (SBR), styrene-isoprene-styrene block copolymer (SIS), styrene-butadiene-styrene block copolymer (SBS), polyisoprene, polyisobutylene (PIB), chloroprene rubber, polybutene, and natural rubber. Synthetic rubber adhesives such as latex and SBR synthetic latex; organosilicon adhesives such as polydimethylsiloxane, polymethylvinylsiloxane, and polymethylphenylsiloxane; and one or more of the following: polyacrylic acid, sodium polyacrylate, partially neutralized polyacrylic acid, N-vinylacetamide-sodium acrylate copolymer, polyvinyl alcohol, polyvinylpyrrolidone, hydroxymethyl cellulose, sodium carboxymethyl cellulose, alginate, sodium alginate, gelatin, guar gum, tragacanth gum, gum arabic, etc., and adhesives made by crosslinking them with metal salts such as aluminum, zinc, magnesium, and calcium; and butylated hydroxytoluene, hydrogenated rosin glycerol ester, etc.

[0143] The content of the binder in the pharmaceutical composition relative to the whole is, for example, 1% by mass or more, preferably 5% by mass or more, and also, for example, 45% by mass or less, preferably 40% by mass or less, further preferably 35% by mass or less, more preferably 30% by mass or less, even more preferably 25% by mass or less, and also, for example, 20% by mass or less, 15% by mass or less, 10% by mass or less, or 5% by mass or less.

[0144] Examples of pH adjusters include inorganic acids and their salts such as phosphoric acid, sodium hydrogen phosphate hydrate, and hydrochloric acid; organic acids and their salts such as citric acid, malic acid, tartaric acid, gluconic acid, and lactic acid; inorganic bases such as sodium hydroxide and potassium hydroxide; organic amines (such as triethanolamine (2,2,2-Nitrilotriethanol) and diisopropanolamine); and their hydrates.

[0145] Specific examples of salts include monovalent metal salts such as potassium and sodium.

[0146] The content of pH adjuster in a pharmaceutical composition can be determined, for example, based on the overall composition of the pharmaceutical composition and the required pH of the pharmaceutical composition.

[0147] Antioxidants are, for example, one or more of the following components selected from ascorbic acid, ascorbyl palmitate, sodium bisulfite, sodium metabisulfite, sodium ethylenediaminetetraacetate, citric acid hydrate, anhydrous citric acid, butylated hydroxytoluene, butylated hydroxyanisole, benzotriazole, propyl gallate, and butylated hydroxytoluene.

[0148] The content of antioxidants in the pharmaceutical composition is, for example, 0.1 to 2% by mass relative to the total pharmaceutical composition.

[0149] Cooling agents are, for example, one or more selected from the above-mentioned menthol derivatives such as l-menthol, terpenes such as camphor, peppermint oil and eucalyptus oil.

[0150] The content of the cooling agent in the pharmaceutical composition is, for example, 0.1 to 3% by mass relative to the total pharmaceutical composition.

[0151] Examples of surfactants include, for example, nonionic surfactants; anionic surfactants, cationic surfactants, and other ionic surfactants; and amphoteric surfactants.

[0152] Nonionic surfactants include, for example, polyol fatty acid esters or polyol alkyl ethers selected from propylene glycol monofatty acid esters, ethylene glycol monofatty acid esters, glycerol monofatty acid esters, polyglycerol fatty acid esters, sorbitan fatty acid esters, sucrose fatty acid esters, methyl glucoside fatty acid esters, alkyl polyglucosides, polyethylene glycol fatty acid esters (e.g., polyethylene glycol monostearate), polyoxyethylene alkyl ethers (polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oil ether, polyoxyethylene sorbitan ether, etc.), polyoxyethylene alkylphenyl ethers, polyoxyethylene phytosterols, polyoxyethylene phytosterols, polyoxyethylene polyoxypropylene alkyl ethers, etc. Polyoxyethylene mono-fatty acid esters, polyethylene glycol di-fatty acid esters, polyoxyethylene glycerol fatty acid esters, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80 and other polyoxyethylene dehydrated sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene methyl glucoside fatty acid esters, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60 and other polyoxyethylene hydrogenated castor oils, polyoxyethylene castor oil, polyoxyethylene vegetable oil, polyoxyethylene alkyl ether fatty acid esters, polyoxyethylene polyoxypropylene glycol and other ether esters, one or more of these.

[0153] The content of nonionic surfactant in the pharmaceutical composition is, for example, 0.1 to 20% by mass relative to the whole pharmaceutical composition.

[0154] Among ionic surfactants, anionic surfactants include, for example, alkyl sulfates such as sodium dodecyl sulfate and sodium hexadecyl sulfate. Specific examples of salts include monovalent metal salts such as potassium and sodium.

[0155] Examples of stabilizers include sodium ethylenediaminetetraacetate and its hydrate, hydrated silica, and zinc stearate. The content of the stabilizer in the pharmaceutical composition is, for example, 0.001 to 1.5% by mass relative to the total pharmaceutical composition.

[0156] Examples of colorants include titanium dioxide. The content of the colorant in the pharmaceutical composition is, for example, 0.001 to 2% by mass relative to the total pharmaceutical composition.

[0157] Examples of fillers include talc. The content of the filler in the pharmaceutical composition is, for example, 1 to 20% by mass relative to the total pharmaceutical composition.

[0158] Examples of crosslinking agents include dried aluminum hydroxide gel.

[0159] Examples of gelling agents include sodium stearate. The content of the gelling agent in the pharmaceutical composition is, for example, 1 to 20% by mass relative to the total pharmaceutical composition.

[0160] Examples of rosin derivatives, such as hydrogenated rosin glycerol esters, can be used as thickeners. The content of the thickener in the pharmaceutical composition is, for example, 3 to 20% by mass relative to the total pharmaceutical composition.

[0161] (pH)

[0162] The pH of the pharmaceutical composition is, for example, 3.5 or higher, preferably 4.0 or higher, more preferably 5.0 or higher, even more preferably 6.0 or higher, and also, for example, 8.5 or lower, preferably 8.0 or lower, more preferably 7.5 or lower. This reduces irritation to the skin and other application sites.

[0163] Specifically, the pH of the pharmaceutical composition can be measured at 25°C using a commercially available pH meter.

[0164] <In the case of solid compositions>

[0165] As one embodiment of this invention, the following mainly illustrates the case where the pharmaceutical composition is a solid composition. Examples of solid compositions include oral solid dosage forms.

[0166] When a pharmaceutical composition is a solid composition, it may contain ingredients other than loxoprofen, as shown below.

[0167] For example, from the perspective of inhibiting gastric mucosal damage, the solid composition may further contain an acid suppressant.

[0168] The acid suppressant is, for example, a metal-based alkaline compound or other metal compound, more specifically, an inorganic salt of divalent or higher metals selected from magnesium silicate, magnesium aluminum silicate, magnesium aluminum silicate, magnesium hydroxide, magnesium hydroxide-potassium aluminum sulfate coprecipitate, magnesium carbonate, synthetic hydrotalcite, magnesium aluminum metasilicate, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium aluminum hydroxide, aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate coprecipitate, aluminum hydroxide-magnesium carbonate mixed dried gel, aluminum hydroxide-magnesium carbonate-calcium carbonate coprecipitate, bentonite, calcium silicate, calcium carbonate, precipitated calcium carbonate, dicalcium phosphate, anhydrous dicalcium phosphate, etc.; and an inorganic salt of monovalent metals selected from dried sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium carbonate hydrate, sodium hydrogen phosphate hydrate, anhydrous sodium monohydrogen phosphate, potassium hydroxide, potassium bicarbonate, potassium carbonate, etc.

[0169] Metals with a valence of divalent or higher are selected from, for example, magnesium, calcium, and aluminum. Additionally, monovalent metals are selected from, for example, potassium and sodium.

[0170] In addition, the solid composition may contain a pharmaceutically acceptable carrier, such as one or more additives selected from excipients, binders, disintegrants, disintegrant aids, lubricants, flow agents, gloss agents, foaming agents, moisture-proofing agents, surfactants, stabilizers, emulsifiers, antioxidants, fillers, preservatives, sweeteners, flavoring agents, cooling agents, flavorings, fragrances, colorants, bases, coating agents, sugar coatings, plasticizers, dispersants, and defoamers. These may be, for example, pharmaceutical additives used in solid compositions that are already known.

[0171] Examples of excipients include, for example, powdered sugar, gum arabic, gum arabic powder, cocoa butter, caramel, sodium carboxymethyl starch, hydrated silica, anhydrous amorphous silica, xylitol, magnesium aluminum silicate, calcium silicate, magnesium silicate, anhydrous dicalcium phosphate, anhydrous dicalcium phosphate granules, monodicalcium phosphate, dicalcium phosphate hydrate, dicalcium phosphate granules, sodium hydrogen phosphate hydrate, didicalcium phosphate hydrate, crystalline cellulose, crystalline cellulose·sodium carboxymethyl cellulose, crystalline cellulose (microparticles), crystalline cellulose (granules), powdered cellulose, synthetic aluminum silicate, synthetic aluminum silicate·hydroxypropyl starch·crystalline cellulose Vitamin B1, wheat starch, rice flour, rice starch, heavy anhydrous silicic acid, refined white sugar, refined white sugar granules, gelatin, D-sorbitol, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, dextrin, corn starch, corn starch granules, trehalose, silicon dioxide, lactose hydrate, lactose granules, white sugar, potato starch, hydroxypropyl starch, powdered sugar, powdered maltose, powdered reduced maltose syrup, powdered cellulose, pectin, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 60, maltitol, D-mannitol, magnesium aluminum metasilicate, calcium sulfate, glucose, and fructose, one or more of these.

[0172] As a binder, examples include one or more selected from gum arabic, gum arabic powder, plum powder, gelatin, shellac, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, pullulan, povidone, polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, butyl methacrylate-methyl methacrylate copolymer, methylcellulose, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer.

[0173] Examples of disintegrants include, for example, one or more selected from sodium carboxymethyl starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, croscarmellose, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, partially pregelatinized starch and sodium starch glycolate.

[0174] Examples of disintegrating agents include, for example, one or more selected from sodium carboxymethyl starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, crystalline cellulose, sodium bicarbonate, precipitated calcium carbonate, hydroxypropyl starch, polysorbate 40, polysorbate 60, polysorbate 80, polyethylene glycol 1500, and polyethylene glycol 4000.

[0175] As a lubricant, examples include one or more selected from magnesium stearate, calcium stearate, zinc stearate, talc, sucrose fatty acid ester, glycerol fatty acid ester, polyethylene glycol, hydrogenated oil, and sodium stearate fumarate.

[0176] As a flow agent, examples include one or more selected from synthetic aluminum silicate, heavy anhydrous silicate, magnesium aluminum hydroxide, stearic acid, calcium stearate, magnesium stearate, tricalcium phosphate, talc, and dicalcium phosphate granules.

[0177] As a glossing agent, examples include one or more selected from carnauba wax, refined beeswax, refined shellac, polyethylene glycol 400, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF and beeswax.

[0178] As foaming agents, examples include one or more selected from dry sodium carbonate, tartaric acid, potassium bitartrate, sodium bicarbonate, and anhydrous citric acid.

[0179] As a desiccant, examples include one or more selected from ethyl cellulose, olive oil, dried aluminum hydroxide gel, glycerin, magnesium silicate, hydrogenated oil, synthetic aluminum silicate, sucrose fatty acid ester, stearic acid, magnesium stearate, refined shellac, refined white sugar, talc, neutral anhydrous sodium sulfate, precipitated calcium carbonate, a mixture of fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, and hydroxypropyl methylcellulose 2910, and polyvinyl acetal diethylaminoacetate.

[0180] As surfactants, examples include one or more selected from sucrose fatty acid esters, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearate, polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) diol, polyoxyethylene (105) polyoxypropylene (5) diol, polyoxyethylene (120) polyoxypropylene (40) diol, polyoxyethylene (160) polyoxypropylene (30) diol, polyoxyethylene (10) polyoxypropylene (4) cetyl ether, polysorbate 20, polysorbate 60, polysorbate 80, polyethylene glycol 400, sorbitan monooleate, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, and sodium dodecyl sulfate.

[0181] Examples of stabilizers include, for instance, succinic acid, L-aspartic acid, sodium L-aspartate, DL-alanine, L-alanine, L-arginine, L-arginine hydrochloride, sodium alginate, propylene glycol alginate, benzoic acid, sodium benzoate, ethylenediamine, calcium disodium ethylenediaminetetraacetate, sodium ethylenediaminetetraacetate, sodium ethylenediaminetetraacetate hydrate, tetrasodium ethylenediaminetetraacetate, tetrasodium ethylenediaminetetraacetate tetrahydrate, zinc chloride, ammonium chloride, calcium chloride hydrate, and hexadecylpyridine chloride. Ferric chloride, sodium chloride, magnesium chloride, cysteine ​​hydrochloride, L-histidine hydrochloride, cocoa butter, carboxyvinyl polymer, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, dried sodium carbonate, glycine, glycerol, glycerol fatty acid esters, calcium gluconate hydrate, sodium gluconate, magnesium gluconate, potassium L-glutamate, monosodium L-glutamate, L-glutamic acid, L-lysine, crystalline sodium dihydrogen phosphate, sodium chondroitin sulfate, zinc oxide, L-cysteine, L-cysteine, tartaric acid, sucrose fatty acid esters, stearic acid, refined gelatin, refined soybean lecithin, gelatin, gelatin hydrolysate, sorbitan fatty acid esters, taurine, talc, calcium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate hydrate, magnesium carbonate, natural vitamin E, tocopherol, tocopheryl acetate, lactose, concentrated glycerol, povidone, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearate, polyoxyethylene cetyl ether, polyoxyethylene nonyl ether Polyphenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene (42)polyoxypropylene (67) glycol, polyoxyethylene (54)polyoxypropylene (39) glycol, polyoxyethylene (160)polyoxypropylene (30) glycol, polyoxyethylene (196)polyoxypropylene (67) glycol, polyoxyethylene coconut oil fatty acid glyceride (7E.O.), polysorbate 20, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), poly One or more of the following: ethylene glycol 300, polyethylene glycol 400, polyethylene glycol 4000, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium monohydrogen phosphate, anhydrous sodium dihydrogen phosphate, methylcellulose, l-menthol, glyceryl monostearate, pharmaceutical charcoal, magnesium sulfate hydrate, DL-malic acid, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, L-leucine, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer.

[0182] Examples of emulsifiers include one or more selected from glycerol fatty acid esters, propylene glycol fatty acid esters, polyoxyethylene glycerol fatty acid esters, polyglycerol fatty acid esters, sucrose fatty acid esters, dehydrated sorbitan fatty acid esters, polyoxyethylene dehydrated sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyethylene glycol fatty acid esters, and hydrogenated soybean lecithin.

[0183] As antioxidants, examples include one or more selected from ascorbic acid, L-ascorbic acid stearate, citric acid hydrate, soybean lecithin, natural vitamin E, tocopherol, tocopheryl acetate, ascorbate palmitate, and sodium metabisulfite.

[0184] As fillers, examples include one or more selected from RSS No.1 raw rubber, acrylic grafted starch 1000, titanium dioxide, and dicalcium phosphate.

[0185] As a preservative, examples include one or more selected from benzoic acid, sodium benzoate, ethylparaben, propylparaben, methylparaben, dehydroacetic acid, sodium dehydroacetate, sorbic acid, and phenoxyethanol.

[0186] As a sweetener, examples include one or more selected from aspartame, acesulfame potassium, sweet tea, sweet tea powder, reduced maltose syrup, licorice, licorice extract, licorice powder, xylitol, dipotassium glycyrrhizate, disodium glycyrrhizate, saccharin, sodium saccharin hydrate, sucralose, stevia extract, purified stevia extract, refined white sugar, fructose, white sugar, maltitol, D-mannitol, and erythritol.

[0187] As flavoring agents, examples include one or more selected from sodium chloride, orange, orange peel oil, cocoa powder, fructose, caramel, xylitol, calcium citrate, citrate hydrate, sodium citrate hydrate, L-glutamic acid, monosodium L-glutamate, grapefruit extract, brown sugar, saccharin, sodium saccharin hydrate, tartaric acid, D-tartaric acid, potassium hydrogen tartrate, sodium DL-tartrate, sucralose, stevia extract, purified stevia extract, Swertia japonica, D-sorbitol, tannic acid, trehalose hydrate, fructooligosaccharides, powdered sugar, peppermint powder, D-mannitol, dl-menthol, l-menthol, menthol powder, green tea powder, DL-malic acid, sodium DL-malate, lemon oil, and rose oil.

[0188] As a cooling agent, examples include one or more selected from anise oil, d-camphor, dl-camphor, cinnamon oil, peppermint water, peppermint oil and l-menthol.

[0189] As a flavoring agent, examples include one or more selected from orange flavoring, guarana extract, sweet orange, strawberry, brown sugar flavoring, strawberry flavoring, cherry flavoring, banana powder flavoring, peach flavoring, fruit flavoring, peppermint, melon powder flavoring, L-menthol, and peppermint oil.

[0190] As a fragrance agent, examples include one or more selected from fennel powder, fennel oil, ethyl vanillin, d-camphor, dl-camphor, spearmint oil, turpentine oil, pineapple powder fragrance 51357, pineapple powder fragrance 59492, peppermint water, peppermint oil, vanilla powder fragrance 54286, vanillin, bergamot oil, d-borneol, dl-borneol, dl-menthol, l-menthol, eucalyptus oil, rose water, and rose oil.

[0191] As coloring agents, examples include one or more selected from yellow iron oxide, yellow ferric oxide, orange extract, brown iron oxide, carbon black, caramel, β-carotene, gold leaf, black iron oxide, titanium dioxide, ferric oxide, diazo yellow, edible blue 1, edible yellow 4, edible yellow 5, edible blue 2 aluminum lake, edible yellow 4 aluminum lake, edible red 2, edible red 3, edible red 102, ferric oxide-glycerol suspension, sodium copper chlorophyllin, copper chlorophyll, phenol red, malachite green, methylene blue, medicinal charcoal, riboflavin, riboflavin butyrate, sodium riboflavin phosphate, green tea powder, and rose oil.

[0192] Examples of base agents include, for instance, gum arabic powder, pregelatinized starch, ethyl cellulose, cocoa butter, carnauba wax, carboxyvinyl polymers, carboxymethyl cellulose, sodium carboxymethyl cellulose, reduced maltose syrup, dried aluminum hydroxide gel, agar, agar powder, xanthan gum, glycine, glycerol, glyceryl fatty acid esters, crystalline cellulose, hydrogenated oil, titanium dioxide, tartaric acid, sucrose fatty acid esters, silicone oil, stearic acid, magnesium stearate, gelatin, D-sorbitol, talc, calcium carbonate, corn starch, lactic acid, ethyl lactate, calcium lactate hydrate, lactic acid-glycolic acid copolymer, concentrated glycerol, potato starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, pullulan. The following are one or more of the following: polysaccharides, pectin, povidone, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), microcrystalline wax, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, polyethylene glycol 20000, sodium stearate, glyceryl monostearate, sorbitan monostearate, squalene monostearate, propylene glycol monostearate, polyethylene glycol monostearate, sodium dodecyl sulfate, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer.

[0193] Examples of coating agents include, for instance, those selected from ethyl acrylate-methyl methacrylate copolymer dispersions, aminoalkyl methacrylate copolymers E, aminoalkyl methacrylate copolymers RS, gum arabic, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersions, carbamate wax, carboxyvinyl polymers, gold foil, silver foil, triethyl citrate, glycerol, glycerol fatty acid esters, hydrogenated oil, titanium dioxide, sucrose fatty acid esters, stearyl alcohol, stearic acid, magnesium stearate, refined gelatin, refined shellac, gelatin, D-sorbitol, talc, calcium carbonate, magnesium carbonate, medium gold foil, precipitated calcium carbonate, concentrated glycerol, white shellac, hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose 2910-titanium dioxide-polyethylene glycol 400 mixture, hydroxypropyl methylcellulose, fumaric acid-stearic acid-polyvinyl acetal diethylaminoacetate-hydroxypropyl methylcellulose 2910 Mixtures, pullulan, polysorbate 80, polyvinyl acetal diethylaminoacetate, povidone, polyvinyl alcohol (partially saponified), polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, polyethylene glycol 20000, polyethylene glycol 35000, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium aluminum metasilicate, methyl acrylate-methacrylic acid-methyl methacrylate copolymer, methylcellulose, 2-methyl-5-vinylpyridine methacrylate-methacrylic acid copolymer, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, and one or more of the following: polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer.

[0194] As a sugar coating agent, examples include one or more selected from gum arabic, gum arabic powder, ethyl cellulose, carnauba wax, sodium carboxymethyl cellulose, titanium dioxide, stearic acid, polyoxyethylene (40) stearate, refined gelatin, refined shellac, refined white sugar, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, white sugar, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, pullulan, povidone, polyvinyl alcohol (partially saponified), polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer.

[0195] As plasticizers, examples include one or more selected from triethyl citrate, glycerol, glyceryl fatty acid esters, D-sorbitol, medium-chain triglycerides, triacetin, concentrated glycerol, castor oil, polyoxyethylene hydrogenated castor oil 60, propylene glycol, polyoxyethylene (105)polyoxypropylene (5) glycol, polysorbate 80, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, glyceryl monostearate, isopropyl linoleate, and liquid paraffin.

[0196] Examples of dispersants include, for instance, aminoalkyl methacrylate polymers (RS), gum arabic, gum arabic powder, carboxyvinyl polymers, sodium carboxymethyl starch, agar powder, citric acid hydrate, sodium citrate hydrate, glycerol, glycerol fatty acid esters, magnesium silicate, light alumina, crystalline cellulose, titanium dioxide, sucrose fatty acid esters, stearic acid, magnesium stearate, D-sorbitol, soybean lecithin, low-substituted hydroxypropyl cellulose (as an in-particulate component), dextrin, corn starch, lactose hydrate, concentrated glycerol, potato starch, hydroxyethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and povidone. One or more of the following: polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polysorbate 20, polysorbate 60, polysorbate 80, microcrystalline wax, polyethylene glycol 300, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, anhydrous sodium citrate, magnesium aluminum metasilicate, methylcellulose, glyceryl monooleate, sorbitan monooleate, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, and sodium dodecyl sulfate.

[0197] Examples of defoaming agents include, for example, one or more selected from ethanol, glycerol fatty acid esters, dimethyl polysiloxane (for oral administration), sucrose fatty acid esters, organosilicon defoamers, silicone oil, dehydrated sorbitan fatty acid esters, and polysorbate 80.

[0198] In addition, the solid composition may be further formulated with active ingredients other than loxoprofen, within the scope of not impairing the effect of the present invention. For example, it may be selected from one or more of antipyretic analgesics, antitussives and expectorants, antihistamines, anti-inflammatory agents, anticholinergic agents, vitamins, xanthine derivatives and sedatives. If there are incompatibilities among them, they may be granulated or otherwise formulated separately.

[0199] Examples of antipyretic analgesics include, for example, one or more selected from aspirin, aspirin aluminum, acetaminophen, ethazamide, sasapyrine, salicylamide, lactylphenetidin, ibuprofen, isopropylantipyrine, pranoprofen, diclofenac sodium, mefenamic acid, indometacin farnesil, acemetacin, edodelac, naproxen, meloxicam, celecoxib, sodium salicylate, and tiaramide hydrochloride.

[0200] Examples of antitussive and expectorant agents include, for instance, those selected from codeine, codeine phosphate hydrate, dihydrocodeine, dihydrocodeine phosphate, tipepidine citrate, tipepidine hibenzate, dibunate sodium, dimemorfan phosphate, dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalate, alloclamide hydrochloride, cloperastine hydrochloride, and cloperastine fendestine. fendizoate, pentoxyverine citrate, noscapine, noscapine hydrochloride, trimetoquinol hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-Methylephedrine hydrochloride, dl-Methylephedrine hydrochloride, dl-Methylephedrine saccharinate, guaiafenesin, potassium guaiacolsulfonate, potassium cresolsulfonate cresolsulphonate, L-carbocisteine, ambroxol hydrochloride, bromhexine hydrochloride, and L-ethyl cysteine ​​hydrochloride.One or more of the following: hydrochloride.

[0201] Examples of antihistamines include, for example, those selected from Azelastine Hydrochloride, Alimemazine Tartrate, Ebastine, Epinastine Hydrochloride, Emedastine Difumarate, Oxatomide, Olopatadine Hydrochloride, Carbinoxamine, Clemastine fumarate, Diphenyldisulfonate, Carbinoxamine maleate, d-Chlorpheniramine maleate, dl-Chlorpheniramine maleate, Ketotifen Fumarate, and Diphenylpyraline Hydrochloride. hydrochloride, Diphenylpyralineteoclate, Diphenhydramine Hydrochloride, Diphenhydramine salicylate, Diphenhydramine tannate, Triprolidine Hydrochloride, Tripelennamine Hydrochloride, Thonzylamine Hydrochloride, Fexofenadine, Fenethazine Hydrochloride, Promethazine Hydrochloride, Promethazine, Mequitazine, Methdilazine Hydrochloride, Loratadine, isopentyl hydrochloride, Difeterol Hydrochloride Hydrochloride, Methdilazine Hydrochloride, Mebhydrolin Naphthalene DisulfonateOne or more of napadisylate, promethazine methylenedisalicylate, and difeterol phosphate.

[0202] As anti-inflammatory agents, examples include one or more selected from glycyrrhizic acid, its derivatives and their salts (e.g., dipotassium glycyrrhizate, monoammonium glycyrrhizate, etc.); and tranexamic acid.

[0203] Examples of anticholinergic agents include, for example, those selected from scopolamine hydrobromide, datura extract, methyl scopolamine bromide, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, scopolamine butyl bromide, belladonna alkaloid, belladonna extract, belladonna total alkaloid, isopropamide iodide, diphenylpiperidine methyl dioxolane iodide, scopolamine extract, and scopolamine root. One or more of the following: root and Scopolia root totalalkaloid citrate.

[0204] Examples of vitamins include those selected from vitamin A, vitamin C, vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin P, vitamin E, hesperidin, niacin, niacinamide, panthenol, calcium pantothenate, sodium pantothenate, biotin, a mixture of potassium and magnesium aspartate, inositol hexanicotinate, ursodeoxycholic acid, L-cysteine, L-cysteine ​​hydrochloride, orotic acid, γ-oryzanol, calcium glycerophosphate, calcium gluconate, gluconolactone, glucuronamide, and sodium chondroitin sulfate. Sulfate, carrot, Job's tears and iodic acid are one or more of the following:

[0205] Examples of xanthine derivatives include, for example, one or more selected from caffeine hydrate, anhydrous caffeine, sodium caffeine benzoate and caffeine citrate.

[0206] As a sedative, examples include at least one selected from allyl isopropyl acetylurea and bromoisovalerate.

[0207] The solid composition preferably further comprises one or more selected from hydroxypropyl cellulose, carboxymethyl cellulose and their salts, and metal stearate salts. This results in good formability, disintegration properties, and tableting properties of the solid composition.

[0208] Examples of metal stearate salts include divalent metal salts such as magnesium stearate and calcium stearate, and trivalent metal salts such as aluminum monostearate.

[0209] (Pharmaceutical preparations)

[0210] The dosage forms of pharmaceutical preparations are selected from, for example, topical preparations for use on the skin (including the scalp) or mucous membranes (preferably excluding preparations for use on the eyes such as eye drops), oral preparations (solid preparations such as tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, etc.; liquid preparations), and preparations for use in the oral cavity (oral tablets, lozenges, sublingual tablets, buccal tablets, oral patches, gel-based preparations, etc.).

[0211] The dosage form of pharmaceutical preparations can be, for example, the dosage form included in the General Principles of Preparations in the 18th revised edition of the Japanese Pharmacopoeia.

[0212] The pharmaceutical preparation is preferably a topical preparation, and more preferably a topical skin preparation. This allows for convenient and selective application to the desired site.

[0213] Examples of topical agents include liquids (lotions, liniments, etc.), gels, creams, sprays, aerosols, ointments, topical solids (sticks, hard gels), and patches (dapoxetines, adhesive patches, etc.).

[0214] From the perspective of achieving the desired performance more appropriately, the topical agent is preferably selected from any one of liquid, gel, cream, spray, aerosol, ointment and hard gel.

[0215] The manufacturing method of the pharmaceutical composition includes, for example, a step of obtaining the pharmaceutical composition by combining raw materials containing loxoprofen. The pharmaceutical composition can be formulated, for example, according to its dosage form. For example, the pharmaceutical composition can be obtained according to the methods described in the General Principles of Formulations, etc., of the 18th revised edition of the Japanese Pharmacopoeia, depending on the dosage form and components of the pharmaceutical composition. Furthermore, topical solid dosage forms can be obtained, for example, using the methods described in International Publication No. 2024 / 158041.

[0216] Additionally, the manufacturing method of a pharmaceutical preparation includes, for example, a step of preparing a pharmaceutical composition and a packaging body, and a step of covering the pharmaceutical composition with the packaging body. In the step of covering the pharmaceutical composition, the pharmaceutical composition is covered in a manner in which the packaging body has at least one of the configurations of methods 1 and 2 in at least a portion of the area covering the pharmaceutical composition.

[0217] The embodiments of the present invention have been described above, but they are merely examples of the present invention, and various configurations other than those described above may also be used.

[0218] Example

[0219] The following examples and comparative examples illustrate this embodiment in detail, but this embodiment is not limited to these examples.

[0220] (Formulas 1-6)

[0221] Liquid compositions for each example were prepared according to the ingredients and formulations listed in Table 1. Specifically, ethanol was measured and placed in a beaker, and loxoprofen sodium hydrate and menthol were added and stirred. After confirming dissolution, the other ingredients listed in Table 1 were added and stirred.

[0222] [Table 1]

[0223]

[0224] (Manufacturing and evaluation of pharmaceutical preparations)

[0225] Liquid compositions of Formulation Examples 1-6 (Formulation Example 6 being a control example) were contained in packaging to prepare sealed pharmaceutical preparations. The formation of decomposition products of loxoprofen was evaluated using the following methods. The results of pharmaceutical preparations containing pharmaceutical compositions of Formulation Examples 1-5 are shown in Tables 2-6, respectively.

[0226] (Production of packaging materials and pharmaceutical preparations)

[0227] Prepare the following 6 types of packaging containers. Obtain a pharmaceutical preparation by containing 40g of each formulation pharmaceutical composition in packaging containers 1 to 6.

[0228] • Packaging 1: A package consisting of a transparent glass bottle (Made by Maruemu, Mighty Vial No. 7, 1.3mm thick, the same applies below) and its special cap (black) wrapped entirely with a transparent film (Made by Ehime Shiko, NEW CELLOPHANE, 20μm thick).

[0229] • Packaging 2: A packaging body consisting of a transparent glass bottle and its special cap (black) entirely wrapped with a blue film (manufactured by Ehime Shiko, NEW CELLOPHANE, 20μm thick).

[0230] • Packaging body 3: A packaging body consisting of a transparent glass bottle and its special cap (black) wrapped entirely with a green film (manufactured by Ehime Shiko, NEW CELLOPHANE, 20μm thick).

[0231] • Packaging body 4: A packaging body consisting of a transparent glass bottle and its special cap (black) wrapped entirely with a yellow film (manufactured by Ehime Shiko, NEW CELLOPHANE, 20μm thick).

[0232] • Packaging Component 5: A packaging component consisting of a transparent glass bottle and its special cap (black) entirely wrapped with a red film (manufactured by Ehime Shiko, NEW CELLOPHANE, 20μm thick).

[0233] • Packaging Body 6: A packaging body consisting of a transparent glass bottle and its special cap (black) entirely wrapped with aluminum film (manufactured by Ehime Shiko, NEW CELLOPHANE, 20μm thick).

[0234] For the optical properties of packages 1–6, the transmittance of the packages to light with wavelengths of 300–800 nm was measured at 0.5 nm intervals using a spectrophotometer (Shimadzu UV-2700 UV-Vis spectrophotometer) with air as a control. The average transmittance and maximum transmittance were determined by calculating the average and maximum values ​​of the obtained transmittance. The results are shown in Tables 2–7.

[0235] (Evaluation of pharmaceutical preparations)

[0236] The obtained pharmaceutical preparation was irradiated with a total illuminance of 1.2 million lux·hr using a light source (D65 lamp).

[0237] The formation of decomposition products in the irradiated pharmaceutical preparation was determined by the method described later. Based on the amount of three representative decomposition products tested—decomposition product 1 (relative retention time (RRT) 1.17 relative to loxoprofen), decomposition product 2 (RRT 1.37), and decomposition product 3 (RRT 1.44)—the following criteria were used for evaluation, with A being considered acceptable. The results for formulations 1–5 are summarized in Tables 2–6.

[0238] A: The amount of decomposition products 1 to 3 produced is all below 0.2%.

[0239] B: The amount of at least one of decomposition products 1 to 3 generated is greater than 0.2%.

[0240] (Methods for determining decomposition products)

[0241] For the decomposition products, the percentage of peak area of ​​each decomposition product relative to the peak area of ​​loxoprofen in the standard solution was calculated using liquid chromatography.

[0242] Detector: Ultraviolet spectrophotometer (measurement wavelength 210 nm)

[0243] Column: A column made of octadecylsilane-bonded silica gel with a particle size of 5 μm, packed in a stainless steel tube with an inner diameter of 4.6 mm and a length of 15 cm.

[0244] [Table 2]

[0245]

[0246] [Table 3]

[0247]

[0248] [Table 4]

[0249]

[0250] [Table 5]

[0251]

[0252] [Table 6]

[0253]

[0254] [Table 7]

[0255]

[0256] According to Tables 1 to 7, it can be seen that in pharmaceutical preparations having at least one of the components of methods 1 and 2, the generation of decomposition products from loxoprofen sodium hydrate contained in the liquid composition can be appropriately suppressed.

[0257] The following are examples of pharmaceutical formulations.

[0258] (Formulation examples 1A-6A, 1B-6B, 1C-6C, 1D-6D, 1E-6E: lotion)

[0259] (Formulation Examples 1A-6A)

[0260] The pharmaceutical composition can be prepared according to the composition shown in Table 8, based on the "External Liquids" and "Lotions" sections of the General Principles of Preparations in the 18th Revision of the Japanese Pharmacopoeia [3], and contained in the containers listed in Table 8 to obtain the preparations of each example.

[0261] [Table 8]

[0262]

[0263] (Formulation examples 1B-6B, 1C-6C, 1D-6D, 1E-6E)

[0264] For the same composition as formulations 1A to 6A, the formulations of each example can be manufactured by replacing the blue translucent polyolefin container with an average transmittance of 55.0% or less in the wavelength region of 550 to 600 nm as described in Table 8 with the following containers.

[0265] Formulation Examples 1B–6B: Green, semi-transparent polyolefin container (the average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%).

[0266] Formulation Examples 1C–6C: Partially translucent polyolefin containers (the average light transmittance of a portion of the container in the 550–600 nm wavelength region is less than 55.0%)

[0267] Formulation examples 1D-6D: Semi-transparent PET containers (the average transmittance of the packaging body in the wavelength region of 550-600nm is less than 55.0%).

[0268] Formulation Examples 1E–6E: Partially translucent PET containers (the average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%).

[0269] (Formulation examples 7A-11A, 7B-11B, 7C-11C, 7D-11D: gel)

[0270] (Formulation Examples 7A-11A)

[0271] Pharmaceutical compositions can be prepared by combining the ingredients according to the composition shown in Table 9, based on the "Gel" section of the General Rules for Preparations in the 18th Revision of the Japanese Pharmacopoeia [3], and contained in the containers listed in Table 9 to obtain the preparations of each example.

[0272] [Table 9]

[0273]

[0274] (Formulation examples 7B-11B, 7C-11C, 7D-11D)

[0275] For compositions identical to formulations 7A to 11A, the container composition and material can be changed from a blue translucent polyolefin tube with an average transmittance of less than 55.0% in the wavelength region of 550 to 600 nm to the following containers.

[0276] Formulation Examples 7B–11B: Green, semi-transparent polyolefin container (the average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%).

[0277] Formulation Examples 7C-11C: Partially translucent polyolefin containers (the average light transmittance of a portion of the container in the 550-600 nm wavelength region is less than 55.0%)

[0278] Formulation Examples 7D-11D: Partially translucent polyolefin container (the portion of the container has an average light transmittance of less than 55.0% in the wavelength region of 550-600 nm), the remainder being a laminated tube made of aluminum and polyolefin.

[0279] (Formulation examples 12A-16A, 12B-16B, 12C-16C, 12D-16D, 12E-16E, 12F-16F, 12G-16G: poultices)

[0280] (Formulation Examples 12A-16A)

[0281] The pharmaceutical composition can be prepared according to the composition shown in Table 10, based on the "Patches" and "Patches" sections of the General Principles of Preparations in the 18th Revision of the Japanese Pharmacopoeia [3], and contained in the container listed in Table 10 to obtain the preparations of each example.

[0282] [Table 10]

[0283]

[0284] (Formulation examples 12B-16B, 12C-16C, 12D-16D, 12E-16E, 12F-16F, 12G-16G)

[0285] For compositions identical to formulations 12A to 16A, the container composition and material can be changed from a blue semi-transparent polyolefin bag with an average transmittance of less than 55.0% in the wavelength region of 550 to 600 nm to the following containers.

[0286] Formulation Examples 12B-16B: Semi-transparent polyolefin bags (the average transmittance of the packaging in the wavelength region of 550-600 nm is less than 55.0%)

[0287] Formulation Examples 12C–16C: Semi-transparent nylon bags (the average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%)

[0288] Formulation examples 12D-16D: Semi-transparent polyvinyl chloride bag (the average transmittance of the packaging body in the wavelength region of 550-600nm is less than 55.0%)

[0289] Formulation Examples 12E–16E: Partially translucent (average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%) polyolefin bags, the remainder being aluminum foil bags.

[0290] Formulation examples 12F–16F: Partially translucent PET bags (average transmittance of the packaging in the 550–600 nm wavelength region is less than 55.0%), the remainder being aluminum foil bags.

[0291] Formulation examples 12G–16G: Partially translucent nylon bags (average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%), the remainder being aluminum foil bags.

[0292] (Formulation examples 17A-26A, 17B-26B, 17C-26C, 17D-26D, 17E-26E, 17F-26F, 17G-26G: adhesive patches)

[0293] (Formulation Examples 17A-26A)

[0294] The pharmaceutical composition can be prepared according to the composition shown in Table 11, based on the "Patches" and "Adhesive Patches" section of the General Rules for Preparations in the 18th Revision of the Japanese Pharmacopoeia [3], and contained in the containers listed in Table 11 to obtain the preparations of each example.

[0295] [Table 11]

[0296]

[0297] (Formulation examples 17B-26B, 17C-26C, 17D-26D, 17E-26E, 17F-26F, 17G-26G)

[0298] For compositions identical to formulations 17A to 26A, the container composition and material can be changed from a blue translucent polyolefin bag with an average transmittance of 55.0% or less in the wavelength region of 550 to 600 nm to the following containers.

[0299] Formulation Examples 17B–26B: Semi-transparent polyolefin bags (the average transmittance of the packaging in the wavelength region of 550–600 nm is less than 55.0%)

[0300] Formulation Examples 17C–26C: Semi-transparent nylon bags (the average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%)

[0301] Formulation Examples 17D-26D: Semi-transparent PVC bag (the average transmittance of the packaging body in the wavelength region of 550-600nm is less than 55.0%)

[0302] Formulation Examples 17E–26E: Partially translucent (average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%) polyolefin bags, the remainder being aluminum foil bags.

[0303] Formulation Examples 17F–26F: Partially translucent PET bags (average transmittance of the packaging in the 550–600 nm wavelength region is less than 55.0%), the remainder being aluminum foil bags.

[0304] Formulation examples 17G–26G: Partially translucent nylon bags (average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%), the remainder being aluminum foil bags.

[0305] (Formulation examples 27A-31A, 27B-31B, 27C-31C, 27D-31D, 27E-31E: rod-shaped formulations (hard gel formulations))

[0306] (Formulation Examples 27A-31A)

[0307] Pharmaceutical compositions can be prepared by combining the components as shown in Table 12. Specifically, a mixture containing the active ingredient, a base ingredient, and additives as needed is stirred under heat until homogeneous, then mixed with a solvent ingredient and cooled to solidify to obtain a pharmaceutical composition. The resulting pharmaceutical composition is contained in the containers listed in Table 12 to obtain the formulations of each example.

[0308] [Table 12]

[0309]

[0310] (Formulation examples 27B-31B, 27C-31C, 27D-31D, 27E-31E)

[0311] For compositions identical to formulations 27A to 31A, the container composition and material can be changed from a blue translucent polyolefin container with an average transmittance of less than 55.0% in the wavelength region of 550 to 600 nm to the following containers.

[0312] Formulation Examples 27B–31B: Green, semi-transparent polyolefin container (the average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%).

[0313] Formulation Examples 27C–31C: Partially translucent polyolefin containers (the average light transmittance of a portion of the container in the 550–600 nm wavelength region is less than 55.0%)

[0314] Formulation Examples 27D-31D: Semi-transparent PET containers (the average transmittance of the packaging body in the wavelength region of 550-600nm is less than 55.0%).

[0315] Formulation Examples 27E–31E: Partially translucent PET containers (the average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%).

[0316] This application claims priority based on Japanese Patent Application No. 2025-053844, filed on March 27, 2025, the entire contents of which are incorporated herein by reference.

Claims

1. A pharmaceutical preparation comprising: A pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates, and A package containing the pharmaceutical composition; The average transmittance of the packaging body in the wavelength region of 550–600 nm is less than 55.0%.

2. The pharmaceutical preparation according to claim 1, wherein, The maximum transmittance of the packaging body in the wavelength region of 550–600 nm is less than 57.0%.

3. A pharmaceutical preparation, comprising: A pharmaceutical composition containing at least one selected from loxoprofen, its salts, and their hydrates, and A package containing the pharmaceutical composition; The maximum transmittance of the packaging body in the wavelength region of 550-600nm is less than 57.0%.

4. The pharmaceutical preparation according to any one of claims 1 to 3, wherein, The interior of the package is visible.

5. The pharmaceutical preparation according to any one of claims 1 to 4, wherein, The average transmittance of the packaging body in the wavelength region of 600-700 nm is less than 57.0%.

6. The pharmaceutical preparation according to any one of claims 1 to 5, wherein, The maximum transmittance of the packaging body in the wavelength region of 600-700 nm is less than 59.0%.

7. The pharmaceutical preparation according to any one of claims 1 to 6, wherein, The ratio of the transmittance of the packaging at a wavelength of 500 nm to the transmittance at a wavelength of 550 nm, R(500 / 550), is 0.5 to 3.

8. The pharmaceutical preparation according to any one of claims 1 to 7, wherein, The packaging shields ultraviolet rays in the wavelength range below 400nm.

9. The pharmaceutical preparation according to any one of claims 1 to 8, wherein, The packaging material comprises at least one selected from resin materials and metal materials.

10. The pharmaceutical preparation according to any one of claims 1 to 9, wherein, The packaging body is made of polyolefin resin, polyester resin, or aluminum.

11. The pharmaceutical preparation according to any one of claims 1 to 10, wherein, The packaging body is a container.

12. The pharmaceutical preparation according to any one of claims 1 to 10, wherein, The packaging material is a film.

13. The pharmaceutical preparation according to any one of claims 1 to 9, wherein, The packaging material is PTP.

14. The pharmaceutical preparation according to any one of claims 1 to 13, wherein, The pharmaceutical composition is for external use only.

15. The pharmaceutical preparation according to claim 14, wherein, The topical agent is selected from any one of liquid, gel, cream, spray, aerosol, ointment and hard gel.

16. The pharmaceutical preparation according to claim 14 or 15, wherein, The topical agent is a liquid.

17. The pharmaceutical preparation according to claim 16, wherein, The liquid contains at least one selected from water, aliphatic alcohols with 1 to 4 carbon atoms, and polyols.

18. The pharmaceutical preparation according to any one of claims 14 to 17, wherein, The content of loxoprofen, its salts and their hydrates in the pharmaceutical composition, relative to the total pharmaceutical composition, is 0.1% to 10% by mass on an anhydrous basis.

19. The pharmaceutical preparation according to any one of claims 1 to 18, wherein, The pharmaceutical composition further comprises l-menthol.

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