Pharmaceutical composition

Abstract

The objective is to provide a pharmaceutical composition that suppresses changes in the appearance of loxoprofen or its salts. [Solution] The inventors of this invention conducted extensive research to solve this problem and found that by incorporating noscapine, it is possible to suppress the change in appearance of loxoprofen or its salt over time. In other words, the pharmaceutical composition is characterized by containing (A) loxoprofen or a salt thereof, and (B) noscapine or a salt thereof, wherein component (A) accounts for 9 to 90% by mass of the total mass of the pharmaceutical composition. According to the present invention, a pharmaceutical composition containing loxoprofen or a salt thereof can be provided that exhibits excellent storage stability.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition containing loxoprofen or a salt thereof.

Background Art

[0002] Loxoprofen is a kind of non-steroidal anti-inflammatory and analgesic drug (NSAID), and is known to be effective for anti-inflammatory, analgesic, and antipyretic effects in rheumatoid arthritis, osteoarthritis, low back pain, periarthritis of shoulder, cervical spondylosis, toothache, acute upper respiratory tract infection, after surgery, trauma, tooth extraction, etc. (Non-Patent Document 1). Due to its excellent antipyretic and analgesic effects, it is formulated in general cold medicines, antipyretic and analgesic drugs, etc. Examples of pharmaceutical compositions containing loxoprofen include Patent Document 1 and the like. Loxoprofen is known to be easily hygroscopic and to become moist and solidify over time (Non-Patent Document 2).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Non-Patent Documents

[0004]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to provide a pharmaceutical composition in which the appearance change of loxoprofen or a salt thereof is suppressed.

Means for Solving the Problems

[0006] Note: The original text has some consecutive tags without content between them (e.g., - ), which are kept as they are in the translation. If there is any specific meaning or expected content for those tags in the original context, it needs to be further clarified for a more accurate translation. In order to solve the above problems, the inventors conducted various studies and, surprisingly, discovered that by incorporating noscapine, it is possible to suppress the change in appearance of loxoprofen or its salt over time.

[0007] In other words, the present invention is (1) A pharmaceutical composition characterized by containing (A) loxoprofen or a salt thereof, and (B) noscapine or a salt thereof, wherein the content of component (A) is 9 to 90% by mass of the total mass of the pharmaceutical composition. (2) The pharmaceutical composition according to (1), wherein the content ratio of component (A) to component (B) is 0.01 to 10 parts by mass of component (B) per 1 part by mass of component (A), (3) The pharmaceutical composition is a solid dosage form as described in (1) or (2), (4) The pharmaceutical composition according to (3), wherein the solid preparation is a tablet, capsule, granule, powder, pill, or film preparation. (5) (A) Use of noscapine or a salt thereof to suppress changes in the appearance of a pharmaceutical composition containing loxoprofen or a salt thereof, That is the case. [Effects of the Invention]

[0008] The present invention makes it possible to provide an excellent pharmaceutical composition containing loxoprofen or a salt thereof, which suppresses changes in the appearance of loxoprofen or a salt thereof over time. [Modes for carrying out the invention]

[0009] The pharmaceutical compositions containing loxoprofen or a salt thereof according to the present invention will be described in detail below.

[0010] The loxoprofen or salt thereof in the pharmaceutical composition of the present invention includes not only loxoprofen, but also pharmaceutically acceptable salts of loxoprofen, and even solvates with water, alcohol, etc. These are known compounds and can be produced by known methods, or commercially available products can be used. In the present invention, loxoprofen sodium hydrate and loxoprofen sodium dihydrate are preferred as loxoprofen or salt thereof. The content of loxoprofen or salt thereof in the pharmaceutical composition of the present invention is not limited and may be appropriately determined by consideration, for example, depending on the gender, age, symptoms, etc. of the user. The daily dose is preferably 18 to 180 mg on an anhydrous basis, or 20.43 mg to 204.3 mg in dihydrate. The amount of loxoprofen or its salt in the pharmaceutical composition of the present invention is not particularly limited as long as it is in an amount that exhibits its pharmacological effect, but is preferably 9 to 90% by mass, more preferably 9.9 to 90% by mass, even more preferably 10 to 90% by mass, particularly preferably 10 to 85% by mass, and most preferably 10 to 81% by mass, based on the total mass of the pharmaceutical composition.

[0011] The noscapine or salt thereof used in this invention has the chemical formula C 22 H 23The compound indicated by NO7 or a salt thereof may be used alone or in combination of two or more. Such noscapine or salts thereof can be manufactured by known methods or commercially available products can be used. Furthermore, noscapine or salts thereof are not particularly limited as long as they are pharmaceutically acceptable, but examples of salts include salts of inorganic acids such as hydrochloride, hydrobromide, phenolphthalate, and phosphate, and organic acid salts such as acetate, oxalate, malonate, succinate, fumarate, maleate, lactate, malate, citrate, tartrate, and carbonate, and hydrochloride or noscapine is preferred. The noscapine or salts thereof used in the present invention may be anhydrous or hydrated. The content of noscapine or salts thereof in the pharmaceutical composition in the present invention is not limited and may be appropriately considered and determined according to, for example, the gender, age, symptoms, etc. of the person taking the medicine. The daily dose is preferably 4.8 to 1850 mg, more preferably 4.8 to 60 mg, even more preferably 24 to 60 mg, and particularly preferably 24 to 48 mg. The amount of noscapine or its salt contained in the pharmaceutical composition of the present invention (the total amount of noscapine or its salts if two or more are contained, the same applies hereinafter) is not particularly limited as long as it is in an amount that exhibits its pharmacological effect, but is preferably 10 to 91% by mass.

[0012] The mixing ratio of (A) loxoprofen or a salt thereof and (B) noscapine or a salt thereof is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 10 parts by mass, and even more preferably 0.1 to 9.1 parts by mass of (B) per 1 part by mass of component (A).

[0013] In the present invention, (A) loxoprofen or a salt thereof and (B) noscapine or a salt thereof are preferably contained in the pharmaceutical composition in a state of coexistence or contact. Coexistence or contact means a state in which (A) loxoprofen or a salt thereof and (B) noscapine or a salt thereof, or granules containing (A) loxoprofen or a salt thereof and granules containing (B) noscapine or a salt thereof, are mixed without physical / or chemical segregation. Examples include a formulation obtained by mixing component (A) and component (B), a formulation in which component (A) and component (B) are contained in the same granule, a formulation in which either component (A) or component (B) is granulated and the other is included without granulation, and a formulation in which component (A) and component (B) are contained in separate granules. Furthermore, for layering granules, coated tablets, multilayer tablets, etc., in which components (A) and (B) are contained in separate layers and not in the same layer, a formulation in which the layer containing component (A) and the layer containing component (B) are arranged in contact is considered a formulation in which the components are contained in contact. However, this does not exclude the inclusion of components other than components (A) and (B), and the coexistence or contact of other active ingredients or additives is permitted.

[0014] The solid composition of the present invention is not particularly limited as long as it is in a dosage form as specified in the General Rules for Formulations of the Japanese Pharmacopoeia, but is preferably a tablet, powder, fine granules, granules, pill, capsule, or film formulation. Tablets specified in the General Rules for Formulations of the Japanese Pharmacopoeia include orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets and dissolvable tablets, sugar-coated tablets, and laminated tablets. Furthermore, the tablets may be scored, marked, or engraved to improve identification. In addition, the tablets of this formulation may be round tablets or irregularly shaped tablets. The solid composition of the present invention may also be a mini-tablet or a dry syrup.

[0015] The pharmaceutical composition of the present invention may contain other commonly used active ingredients, excipients, disintegrants, binders, fluidizers, lubricants, acidulants, sweeteners, flavoring agents, cooling agents, colorants, foaming agents, surfactants, plasticizers, fragrances, coating agents, etc., within a qualitative and quantitative range that does not impair the effects of the present invention.

[0016] Examples of other active ingredients that can be formulated in the pharmaceutical composition of the present invention include, for example, antipyretics, antihistamines, antitussives, bronchodilators, expectorants, hypnotics, vitamins, amino acids, anti-inflammatory agents, gastric mucosal protectants, crude drugs, traditional Chinese medicine prescriptions, caffeine, etc. The pharmaceutical composition may contain one or more selected from the group consisting of these.

[0017] Examples of excipients that can be formulated in the pharmaceutical composition of the present invention include, for example, lactose, starches, crystalline cellulose, sucrose, sugar alcohols, calcium hydrogen phosphates, etc. Examples of disintegrants include low-substituted hydroxypropyl cellulose, sodium starch glycolate, crospovidone, carmellose, sodium carmellose, calcium carmellose, pregelatinized starch, etc. Examples of binders include hydroxypropyl cellulose, hypromellose, gelatin, pregelatinized starch, polyvinylpyrrolidone, pullulan, etc. Examples of glidants include light anhydrous silicic acid, hydrous silicon dioxide, magnesium aluminometasilicate, etc. Examples of lubricants include sucrose fatty acid esters, hardened oils, stearic acid, magnesium stearate, calcium stearate, etc.

[0018] The pharmaceutical composition of the present invention can be produced by a conventional method, and the method is not particularly limited.

[0019] For example, when the pharmaceutical composition of the present invention is a tablet, after mixing the component (A) and the component (B) with other pharmaceutical active ingredients and additives as described above in a suitable mixer such as a blender to produce a mixed powder for tablets, the mixed powder can be produced by a method of directly compression tableting or a method of compression tableting granules, etc. The method for manufacturing the granules can be a dry granulation method (slug method, roller compactor method) or a wet granulation method, without particular limitation, but preferably the wet granulation method. For the wet granulation method, it can be manufactured by a stirring granulation method, a fluidized bed granulation method, a kneading granulation method, an extrusion granulation method, a rolling granulation method, spray granulation, etc., without particular limitation, but preferably the stirring granulation method, the fluidized bed granulation method, or the kneading granulation method. Also, capsules or tablets can be manufactured by a conventional method using these granules. As the machine for compression tableting of the mixed powder for tablets or the granules of the mixed powder, a single-shot tableting machine, a rotary tableting machine, a wet powder tableting machine, etc. can be used. Also, the package containing the pharmaceutical composition of the present invention is preferably an "airtight container" or a "sealed container" defined in the General Rules of the Japanese Pharmacopoeia, 18th Revision. As the package, either a regular or irregular one can be used. Specifically, for example, bottle packaging (sealed), SP (Strip Package) packaging, PTP (Press Through Package) packaging, pillow packaging, and stick packaging are preferable. In the present invention, a combination of a plurality of these may also be used. Specifically, for example, a form in which it is packaged in a PTP package and further packaged in a pillow package is also included.

[0020] <Test Example> Examples and comparative examples are given below to explain the present invention in more detail, but the present invention is not limited to these examples.

[0021] (Preparation of Solid Composition) (Examples 1 to 6, Comparative Examples 1 to 8, Reference Examples 1 to 2) Weighed each raw material component according to the formulation compositions shown in Tables 1 and 2, added an appropriate amount of water, uniformly mixed them in a mortar, and then passed the whole amount through a sieve (mesh size 710 μm) to obtain a mixture.

[0022] <00,00108>

Table 1

Table 2

[0024] (Evaluation of changes in appearance) The mixtures obtained in Examples 1-6, Comparative Examples 1-8, and Reference Examples 1-2 were visually inspected for caking. The evaluation was performed by comparing samples stored at 65°C for 7 days (packaging: approximately 2.5g / sealed 2K bottle) with the samples immediately after storage. The evaluation was based on a 5-point scale: 0: no caking, 1: slight caking, 2: caking but acceptable, 3: obvious caking, unacceptable, 4: significant caking. The average score was calculated. The results are shown in Tables 3 and 4.

[0025] The solid compositions of Comparative Examples 1 to 8 showed caking, and all of them had high scores for appearance change. Reference Examples 1 and 2, which had a loxoprofen sodium hydrate content of 8.5%, showed low scores for appearance change. In other words, it became clear that caking occurs in compositions containing loxoprofen sodium hydrate when the loxoprofen sodium hydrate content is high. On the other hand, Examples 1 to 6, which contained noscapine in addition to loxoprofen sodium hydrate, showed low scores for appearance change.

[0026] [Table 3]

[0027] [Table 4] [Industrial applicability]

[0028] According to the present invention, it is possible to provide a pharmaceutical composition containing loxoprofen or a salt thereof that exhibits excellent storage stability.

Claims

1. A pharmaceutical composition characterized by containing (A) loxoprofen or a salt thereof, and (B) noscapine or a salt thereof, wherein the content of component (A) is 9 to 90% by mass of the total mass of the pharmaceutical composition.

2. The pharmaceutical composition according to claim 1, wherein the content ratio of component (A) to component (B) is 0.01 to 10 parts by mass of component (B) per 1 part by mass of component (A).

3. The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is a solid dosage form.

4. The pharmaceutical composition according to claim 3, wherein the solid preparation is a tablet, capsule, granule, powder, pill, or film preparation.

5. (A) Use of noscapine or a salt thereof to suppress changes in the appearance of a pharmaceutical composition containing loxoprofen or a salt thereof.

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