JP2007284423A - Pharmaceutical preparation and method for producing the same - Google Patents
Pharmaceutical preparation and method for producing the same Download PDFInfo
- Publication number
- JP2007284423A JP2007284423A JP2007061435A JP2007061435A JP2007284423A JP 2007284423 A JP2007284423 A JP 2007284423A JP 2007061435 A JP2007061435 A JP 2007061435A JP 2007061435 A JP2007061435 A JP 2007061435A JP 2007284423 A JP2007284423 A JP 2007284423A
- Authority
- JP
- Japan
- Prior art keywords
- ibuprofen
- salt
- tranexamic acid
- preparation
- binder
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 239000000825 pharmaceutical preparation Substances 0.000 title abstract description 3
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- 229960000401 tranexamic acid Drugs 0.000 claims abstract description 127
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 118
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 115
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- 229910052708 sodium Inorganic materials 0.000 description 1
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- GQTHJBOWLPZUOI-FJXQXJEOSA-M sodium D-pantothenate Chemical compound [Na+].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O GQTHJBOWLPZUOI-FJXQXJEOSA-M 0.000 description 1
- JWBPVFVNISJVEM-UHFFFAOYSA-M sodium caffeine benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1.CN1C(=O)N(C)C(=O)C2=C1N=CN2C JWBPVFVNISJVEM-UHFFFAOYSA-M 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤ならびにその製造方法に関する。 The present invention relates to a preparation containing tranexamic acid or a salt thereof and ibuprofen and a method for producing the same.
トラネキサム酸またはその塩、およびイブプロフェンは、ともに消炎・解熱鎮痛薬の薬効成分として知られており、トラネキサム酸またはその塩、およびイブプロフェンを組み合わせた解熱鎮痛薬や感冒薬等は既に知られている。
「解熱用鎮痛剤」（特許文献１参照）は、イブプロフェンとトラネキサム酸、好ましくはさらにカフェインを含むことを特徴とする解熱鎮痛剤を開示しており、該解熱鎮痛剤の剤形として、錠剤、カプセル剤、丸剤、および散剤等を挙げている。また「イブプロフェン含有解熱鎮痛組成物、及び感冒薬」（特許文献２参照）は、イブプロフェン、トラネキサム酸および／またはその塩、ならびにアスコルビン酸および／またはその塩を含有する解熱鎮痛組成物を開示しており、該解熱鎮痛組成物の製剤の剤形として、錠剤、顆粒剤、散剤、カプセル剤等を挙げている。
しかしながら、これまで、トラネキサム酸とイブプロフェンを含有する製剤特有の問題点等について記載されたものは見当たらない。
Tranexamic acid or a salt thereof and ibuprofen are both known as medicinal ingredients of anti-inflammatory / antipyretic analgesics, and antipyretic analgesics and cold medicines combining tranexamic acid or a salt thereof and ibuprofen are already known.
“An antipyretic analgesic” (see Patent Document 1) discloses an antipyretic analgesic characterized in that it contains ibuprofen and tranexamic acid, preferably caffeine, and the dosage form of the antipyretic analgesic is a tablet. , Capsules, pills, and powders. “Ibuprofen-containing antipyretic analgesic composition and cold medicine” (see Patent Document 2) discloses an antipyretic analgesic composition containing ibuprofen, tranexamic acid and / or a salt thereof, and ascorbic acid and / or a salt thereof. Examples of the dosage form of the antipyretic analgesic composition include tablets, granules, powders, capsules and the like.
However, there have been no reports on the problems peculiar to preparations containing tranexamic acid and ibuprofen.
本発明者らは、トラネキサム酸またはその塩、およびイブプロフェンを含有する錠剤を通常の方法により製造したところ、錠剤の体積が膨張するという問題点を見出した（後記実施例参照）。この問題点は、トラネキサム酸またはその塩、およびイブプロフェンを含有する錠剤をフィルムコーティング錠または糖衣錠とする時、フィルムコーティングまたは糖衣の割れや欠けの原因になり、製剤の安定性の確保に極めて深刻な課題であることを認識するに至った。
すなわち、本発明は、トラネキサム酸またはその塩、およびイブプロフェンを含有する安定した製剤ならびにその製造方法を提供するものである。
The inventors of the present invention have found that when tablets containing tranexamic acid or a salt thereof and ibuprofen are produced by a usual method, the volume of the tablets expands (see Examples below). This problem is extremely serious in ensuring the stability of the formulation, as it may cause cracking or chipping of the film coating or sugar coating when a tablet containing tranexamic acid or its salt and ibuprofen is used as a film coating tablet or sugar coating tablet. It came to recognize that it was a problem.
That is, the present invention provides a stable preparation containing tranexamic acid or a salt thereof and ibuprofen and a method for producing the same.
本発明者らは、かかる課題の解決に向けて鋭意研究を行ってきた。その結果、トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤において、トラネキサム酸またはその塩、およびイブプロフェンを、実質的に互いに接触しないように配合することにより、トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤の体積膨張を防止、ひいては、安定な製剤が実現することを見出し、本発明を完成させるに至った。 The inventors of the present invention have intensively studied to solve such problems. As a result, in a preparation containing tranexamic acid or a salt thereof and ibuprofen, tranexamic acid or a salt thereof and ibuprofen are contained by blending tranexamic acid or a salt thereof and ibuprofen so as not to substantially contact each other. As a result, the present inventors have found that a stable formulation can be realized by preventing volume expansion of the formulation to be produced, and the present invention has been completed.
すなわち本発明は、
１．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤であって、トラネキサム酸またはその塩、およびイブプロフェンが、実質的に互いに接触しないように配合した製剤、
２．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤であって、トラネキサム酸もしくはその塩を含有する粒状物、および／またはイブプロフェンを含有する粒状物を含有する製剤、
３．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤であって、さらに結合剤を含有し、トラネキサム酸またはその塩、およびイブプロフェンが、実質的に互いに接触しないように結合剤を配合した製剤、
４．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤であって、トラネキサム酸もしくはその塩、ならびに結合剤を含有する粒状物、および／またはイブプロフェンならびに結合剤を含有する粒状物を含有する製剤、
５．結合剤が、ポリエチレングリコール類または硬化油である３または４に記載の製剤、
６．結合剤が、マクロゴール６０００である３または４に記載の製剤、
７．トラネキサム酸またはその塩が、トラネキサム酸である１〜６のいずれか１に記載の製剤、
８．製剤の剤形が、錠剤である１〜７のいずれか１に記載の製剤、
９．製剤が、フィルムコーティング錠である１〜８のいずれか１に記載の製剤、
１０．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤の製造方法であって、トラネキサム酸またはその塩、およびイブプロフェンを、実質的に互いに接触しないように配合する工程を含む製剤の製造方法、
１１．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤の製造方法であって、トラネキサム酸またはその塩、およびイブプロフェンのうち、少なくともいずれか一方を造粒する工程を含む製剤の製造方法、
１２．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤の製造方法であって、トラネキサム酸またはその塩、およびイブプロフェンのうち、少なくともいずれか一方を溶融造粒する工程を含む製剤の製造方法、
１３．トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤の製造方法であって、トラネキサム酸またはその塩ならびに結合剤を溶融造粒する工程、およびイブプロフェンならびに結合剤を溶融造粒する工程のうち、少なくともいずれか一方の工程を含む製剤の製造方法、
１４．結合剤が、ポリエチレングリコール類または硬化油である１３に記載の製剤の製造方法、
１５．結合剤が、マクロゴール６０００である１３に記載の製剤の製造方法、
１６．トラネキサム酸またはその塩が、トラネキサム酸である１０〜１５のいずれか１に記載の製剤の製造方法、
１７．製剤の剤形が錠剤である１０〜１６のいずれか１に記載の製剤の製造方法、に関するものである。
That is, the present invention
1. A formulation containing tranexamic acid or a salt thereof and ibuprofen, wherein the formulation is formulated so that tranexamic acid or a salt thereof and ibuprofen do not substantially contact each other,
2. A formulation containing tranexamic acid or a salt thereof and ibuprofen, the granule containing tranexamic acid or a salt thereof, and / or the formulation containing a granule containing ibuprofen,
3. A formulation comprising tranexamic acid or a salt thereof and ibuprofen, further comprising a binder, wherein the formulation is formulated so that tranexamic acid or a salt thereof and ibuprofen do not substantially contact each other,
4). A formulation containing tranexamic acid or a salt thereof and ibuprofen, comprising granule containing tranexamic acid or a salt thereof and a binder, and / or a granule containing ibuprofen and a binder,
5). The preparation according to 3 or 4, wherein the binder is polyethylene glycol or hydrogenated oil,
6). The preparation according to 3 or 4, wherein the binder is Macrogol 6000,
7). The preparation according to any one of 1 to 6, wherein tranexamic acid or a salt thereof is tranexamic acid,
8). The preparation according to any one of 1 to 7, wherein the dosage form of the preparation is a tablet,
9. The preparation according to any one of 1 to 8, wherein the preparation is a film-coated tablet,
10. A method for producing a preparation containing tranexamic acid or a salt thereof and ibuprofen, the method comprising the step of blending tranexamic acid or a salt thereof and ibuprofen so as not to substantially contact each other,
11. A method for producing a preparation containing tranexamic acid or a salt thereof and ibuprofen, the method comprising the step of granulating at least one of tranexamic acid or a salt thereof and ibuprofen,
12 A method for producing a preparation containing tranexamic acid or a salt thereof and ibuprofen, the method comprising the step of melt granulating at least one of tranexamic acid or a salt thereof and ibuprofen,
13. A method for producing a preparation containing tranexamic acid or a salt thereof and ibuprofen, wherein at least one of a step of melt granulating tranexamic acid or a salt thereof and a binder, and a step of melt granulating ibuprofen and a binder A method for producing a preparation comprising either step,
14 14. The method for producing a preparation according to 13, wherein the binder is polyethylene glycol or hydrogenated oil,
15. The method for producing a preparation according to 13, wherein the binder is Macrogol 6000,
16. The method for producing a preparation according to any one of 10 to 15, wherein tranexamic acid or a salt thereof is tranexamic acid,
17. It is related with the manufacturing method of the formulation of any one of 10-16 whose dosage form of a formulation is a tablet.
後記実施例から明らかなように、トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤において、トラネキサム酸またはその塩、およびイブプロフェンを、実質的に互いに接触しないように配合することにより、トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤の体積膨張を防止できる。したがい、本発明により、トラネキサム酸またはその塩、およびイブプロフェンを含有する安定した製剤およびその製造方法を提供することができる。 As will be apparent from the examples below, in a preparation containing tranexamic acid or a salt thereof and ibuprofen, tranexamic acid or a salt thereof and ibuprofen are blended so that they are not substantially in contact with each other. The volume expansion of the preparation containing the salt and ibuprofen can be prevented. Therefore, according to the present invention, a stable preparation containing tranexamic acid or a salt thereof and ibuprofen and a method for producing the same can be provided.
本発明にかかるトラネキサム酸（トランス−４−アミノメチルシクロヘキサンカルボン酸）またはその塩は、公知の化合物であり、その入手方法としては、市販品を用いてもよく、または公知の方法に基づき製造することも可能である。トラネキサム酸の塩としては、塩酸塩、硝酸塩、硫酸塩などの鉱酸塩、フマル酸塩、メタスルホン酸塩等の有機酸、ナトリウム塩、カリウム塩、カルシウム塩、マグネシウム塩等のアルカリ金属塩、アルカリ土類金属塩等を挙げることができる。本発明においては、トラネキサム酸またはその塩としては、トラネキサム酸が好ましい。 Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) or a salt thereof according to the present invention is a known compound, and as a method for obtaining it, a commercially available product may be used, or it is produced based on a known method. It is also possible. The salts of tranexamic acid include mineral acids such as hydrochloride, nitrate and sulfate, organic acids such as fumarate and metasulfonate, alkali metal salts such as sodium, potassium, calcium and magnesium, alkali There may be mentioned earth metal salts. In the present invention, tranexamic acid or a salt thereof is preferably tranexamic acid.
本発明にかかるイブプロフェン（（ＲＳ）−２−（４−イソブチルフェニル）プロパン酸）は、公知の化合物であり、その入手方法としては、市販品を用いてもよく、また公知の方法に基づき製造することも可能である。 Ibuprofen ((RS) -2- (4-isobutylphenyl) propanoic acid) according to the present invention is a known compound, and as a method for obtaining it, a commercially available product may be used, and it is produced based on a known method. It is also possible to do.
本発明の製剤は、トラネキサム酸またはその塩、およびイブプロフェンを含有し、トラネキサム酸またはその塩、およびイブプロフェンが、実質的に互いに接触しないように配合する（した）ことを特徴としている。また、本発明の製剤の製造方法においては、トラネキサム酸またはその塩、およびイブプロフェンを含有し、トラネキサム酸またはその塩、およびイブプロフェンを、実質的に互いに接触しないように配合する工程を含むことを特徴としている。 The preparation of the present invention contains tranexamic acid or a salt thereof and ibuprofen, and is characterized in that tranexamic acid or a salt thereof and ibuprofen are formulated so as not to contact each other substantially. The method for producing the preparation of the present invention comprises tranexamic acid or a salt thereof and ibuprofen, and includes a step of blending tranexamic acid or a salt thereof and ibuprofen so as not to substantially contact each other. It is said.
ここで、「実質的に互いに接触しないように配合する（した）」とは、製剤中でトラネキサム酸またはその塩、およびイブプロフェンの間で相互作用が出現しない程度に接触しないよう配合する（した）ことを意味する。 Here, “formulated so as not to substantially contact each other” means formulated so as not to contact to the extent that no interaction appears between tranexamic acid or its salt and ibuprofen in the preparation. Means that.
本発明において、トラネキサム酸またはその塩、およびイブプロフェンを、実質的に互いに接触しないように配合する方法としては、例えば、（１）トラネキサム酸またはその塩、およびイブプロフェンのうち、少なくともいずれか一方を造粒して粒状物とし、次いで錠剤またはカプセル剤等の製剤とする方法、（２）多層錠または有核錠にて、トラネキサム酸またはその塩、およびイブプロフェンを、互いに接触しないように配合する方法、（３）トラネキサム酸またはその塩、およびイブプロフェンのうち、いずれか一方を含む粒状物をコーティングする方法、（４）トラネキサム酸またはその塩、およびイブプロフェンのうち、少なくともいずれか一方をシクロデキストリンにより包接する方法等がある。 In the present invention, as a method of blending tranexamic acid or a salt thereof and ibuprofen so as not to substantially contact each other, for example, (1) at least one of tranexamic acid or a salt thereof and ibuprofen is prepared. (2) A method of blending tranexamic acid or a salt thereof and ibuprofen so as not to contact each other in a multilayer tablet or a dry tablet, (3) A method of coating a granular material containing any one of tranexamic acid or a salt thereof and ibuprofen; (4) at least one of tranexamic acid or a salt thereof and ibuprofen is included by cyclodextrin. There are methods.
本発明においては、いずれの方法も可能であるが、（１）トラネキサム酸またはその塩、およびイブプロフェンのうち、少なくともいずれか一方を造粒して粒状物とし、次いで錠剤またはカプセル剤等の製剤とする方法が、製造コストの面や製造工程の簡便さ等の面から好ましい。 In the present invention, any method is possible, but (1) at least one of tranexamic acid or a salt thereof and ibuprofen is granulated to form a granular material, and then a formulation such as a tablet or a capsule This method is preferable from the viewpoints of manufacturing cost and simplicity of manufacturing process.
すなわち、本発明においては、（１）トラネキサム酸またはその塩を含有する粒状物、およびイブプロフェンを含有する製剤、（２）イブプロフェンを含有する粒状物、およびトラネキサム酸またはその塩を含有する製剤、（３）トラネキサム酸またはその塩を含有する粒状物、およびイブプロフェンを含有する粒状物を含有する製剤が好ましく、中でもトラネキサム酸またはその塩を含有する粒状物、およびイブプロフェンを含有する粒状物を含有する製剤がより好ましい。 That is, in the present invention, (1) a granule containing tranexamic acid or a salt thereof and a preparation containing ibuprofen, (2) a granule containing ibuprofen, and a preparation containing tranexamic acid or a salt thereof, 3) A granule containing tranexamic acid or a salt thereof and a preparation containing a granule containing ibuprofen are preferable, and a granule containing tranexamic acid or a salt thereof and a preparation containing a granule containing ibuprofen are preferred. Is more preferable.
造粒は、例えば、押し出し造粒、転動造粒、流動層造粒等の湿式造粒、乾式造粒、噴霧造粒、溶融造粒等が挙げられる。本発明の製剤の製造方法においては、トラネキサム酸またはその塩、およびイブプロフェンを造粒するに際して、少なくともいずれか一方を溶融造粒するのが好ましい。ここで溶融造粒とは、原料粉末と、加熱により溶融あるいは軟化する結合剤を混合、攪拌しながら加熱し、次いで冷却することにより造粒する方法のことである。本発明の製剤の製造方法においては、トラネキサム酸またはその塩、およびイブプロフェンのうち、いずれか一方を溶融造粒してもよく、またはトラネキサム酸またはその塩、およびイブプロフェンの両方を、別々に溶融造粒してもよい。いずれか一方を溶融造粒した場合、もう一方を溶融造粒以外の別の造粒を用いてもよい。本発明においては、トラネキサム酸またはその塩を溶融造粒するのが好ましい。 Examples of the granulation include wet granulation such as extrusion granulation, tumbling granulation, and fluidized bed granulation, dry granulation, spray granulation, and melt granulation. In the method for producing the preparation of the present invention, when granulating tranexamic acid or a salt thereof and ibuprofen, it is preferable to melt granulate at least one of them. Here, the melt granulation is a method in which a raw material powder and a binder that is melted or softened by heating are mixed, heated while stirring, and then granulated by cooling. In the preparation method of the present invention, either tranexamic acid or a salt thereof and ibuprofen may be melt-granulated, or both tranexamic acid or a salt thereof and ibuprofen are separately melt-formed. It may be granulated. When either one is melt granulated, another granulation other than melt granulation may be used for the other. In the present invention, it is preferable to melt granulate tranexamic acid or a salt thereof.
また、本発明の製剤の剤形は、錠剤、顆粒剤、細粒剤、カプセル剤等の固形製剤であれば特に制限はないが、錠剤が好ましい。本発明にかかる錠剤は、通常の錠剤（日本薬局方に記載されている有核錠、多層錠等の特殊な錠剤を除いた錠剤。以下、通常錠と称す。）でもよく、またトラネキサム酸またはその塩とイブプロフェンとの実質的な接触を避けるため、多層錠または有核錠としてもよい。 The dosage form of the preparation of the present invention is not particularly limited as long as it is a solid preparation such as a tablet, granule, fine granule or capsule, but a tablet is preferred. The tablet according to the present invention may be a normal tablet (a tablet excluding special tablets such as dry-coated tablets and multilayer tablets described in the Japanese Pharmacopoeia, hereinafter referred to as a normal tablet), or tranexamic acid or In order to avoid substantial contact between the salt and ibuprofen, a multilayer tablet or a dry-coated tablet may be used.
本発明の製剤の剤形が通常錠の場合は、前記造粒にて得られた粒状物と、所望により添加物を公知の方法にて混合し、さらに公知の方法にて圧縮成型すれば、本発明の製剤を得ることができる。すなわち、トラネキサム酸またはその塩を造粒する場合は、トラネキサム酸またはその塩を含有する粒状物、イブプロフェン（所望により造粒してもよい）、および所望により添加物を混合し、次いで圧縮成型することにより、本発明の製剤を得ることができる。また、イブプロフェンを造粒する場合は、イブプロフェンを含有する粒状物、トラネキサム酸またはその塩（所望により造粒してもよい）、および所望により添加物を混合し、次いで圧縮成型することにより、本発明の製剤を得ることができる。 When the dosage form of the preparation of the present invention is a normal tablet, the granule obtained by the granulation and, if desired, the additive are mixed by a known method, and further compression molded by a known method, The preparation of the present invention can be obtained. That is, when granulating tranexamic acid or a salt thereof, a granule containing tranexamic acid or a salt thereof, ibuprofen (which may be granulated if desired), and additives are mixed, and then compression molded. Thus, the preparation of the present invention can be obtained. When granulating ibuprofen, the granular material containing ibuprofen, tranexamic acid or a salt thereof (which may be granulated if desired), and additives are mixed, and then compression molding is performed. The inventive formulation can be obtained.
また、多層錠とは、錠剤の成分を分離して打錠するもので、一方の成分を軽く予圧し、他の成分をその上に加圧成型したものである。本発明の製剤が多層錠の場合、トラネキサム酸またはその塩、およびイブプロフェンは、互いに異なる層に配合されていることが好ましい。この場合、トラネキサム酸またはその塩、イブプロフェンは造粒し、粒状物としてもよい。 The multi-layer tablet is a tablet in which the components of the tablet are separated and compressed, and one component is lightly pre-pressed and the other component is pressure-molded thereon. When the preparation of the present invention is a multilayer tablet, tranexamic acid or a salt thereof, and ibuprofen are preferably blended in different layers. In this case, tranexamic acid or a salt thereof, ibuprofen may be granulated to form a granular material.
また、有核錠とは、中心錠（芯錠、核錠ともいう）の周囲に粉粒体を圧縮成型した錠剤のことである。本発明の製剤が有核錠の場合、トラネキサム酸もしくはその塩、またはイブプロフェンのうちいずれか一方を中心錠に配合し、他方を周囲の粉粒体に配合することが好ましい。この場合、トラネキサム酸またはその塩、イブプロフェンは造粒し、粒状物の形態としてもよい。 The dry-coated tablet is a tablet obtained by compression molding a granular material around a central tablet (also referred to as a core tablet or a core tablet). When the preparation of the present invention is a dry-coated tablet, it is preferable that either one of tranexamic acid or a salt thereof or ibuprofen is blended in the central tablet and the other is blended in the surrounding powder. In this case, tranexamic acid or a salt thereof, ibuprofen may be granulated and may be in the form of granules.
本発明の製剤が錠剤の場合は、コーティング（フイルムコーティング、糖衣）されていることが好ましい。該コーティングは、公知の方法を用いて行なえばよい。トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤において、該製剤がコーティング錠の場合、トラネキサム酸またはその塩、およびイブプロフェンが実質的に接触しないように、トラネキサム酸またはその塩、およびイブプロフェンのうちいずれか一方を、コーティング層に含まれるように配合してもよい。 When the preparation of the present invention is a tablet, it is preferably coated (film coating, sugar coating). The coating may be performed using a known method. In a preparation containing tranexamic acid or a salt thereof and ibuprofen, when the preparation is a coated tablet, any one of tranexamic acid or a salt thereof and ibuprofen so that tranexamic acid or a salt thereof and ibuprofen do not substantially come into contact with each other. Either of them may be blended so as to be included in the coating layer.
本発明の製剤は、前記に挙げた製剤の剤形のいずれにおいても、含有されるトラネキサム酸またはその塩、およびイブプロフェンが実質的に互いに接触しないように、結合剤を加えてもよい。 In the preparation of the present invention, a binder may be added so that the contained tranexamic acid or a salt thereof and ibuprofen do not substantially contact each other in any of the dosage forms of the preparations listed above.
本発明にかかる結合剤は、常温の時に固体であればよく、特に制限されるべきものではない。例えば、ポリエチレングリコール類（例えば、マクロゴール１５００、マクロゴール１５４０、マクロゴール２００００、マクロゴール３５０００、マクロゴール４０００、マクロゴール６０００等）、硬化油、植物性または動物性油脂類（例えば、カルナバロウ、ミツロウ、ナタネ硬化油、ハイエルナタネ硬化油、大豆硬化油、パーム硬化油、ヒマシ硬化油等）、その他脂肪酸エステル類（例えば、グリセリン脂肪酸エステル、ショ糖脂肪酸エステル等）、セルロース類（例えば、結晶セルロース、粉末セルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース等）、糖類（例えば、白糖、乳糖、マンニトール等）、ポリビニルアルコール等が挙げられる。本発明において、トラネキサム酸もしくはその塩および／またはイブプロフェンを溶融造粒する場合、かかる結合剤の融点は、トラネキサム酸もしくはその塩、またはイブプロフェンの融点より低いのが好ましい。本発明において、造粒が溶融造粒の場合は、ポリエチレングリコール類および／または硬化油が好ましく、マクロゴール６０００がさらに好ましい。 The binder according to the present invention is not particularly limited as long as it is solid at room temperature. For example, polyethylene glycols (for example, Macrogol 1500, Macrogol 1540, Macrogol 20000, Macrogol 35000, Macrogol 4000, Macrogol 6000, etc.), hardened oil, vegetable or animal oils (for example, carnauba wax, beeswax) Rapeseed oil, high rapeseed oil, soybean oil, palm oil, castor oil, etc.), other fatty acid esters (eg, glycerin fatty acid ester, sucrose fatty acid ester, etc.), cellulose (eg, crystalline cellulose, Powdered cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc.), sugars (eg, sucrose, lactose, mannitol, etc.), polyvinyl alcohol, and the like. In the present invention, when tranexamic acid or a salt thereof and / or ibuprofen is melt-granulated, the melting point of such a binder is preferably lower than that of tranexamic acid or a salt thereof or ibuprofen. In the present invention, when the granulation is melt granulation, polyethylene glycols and / or hydrogenated oil are preferable, and Macrogol 6000 is more preferable.
これらの結合剤は、いずれも公知の化合物であり、市販のものを用いてもよく、公知の方法を用いて製造することも可能である。 These binders are all known compounds, commercially available ones may be used, and they can be produced using known methods.
本発明の製剤において、トラネキサム酸またはその塩、およびイブプロフェンのうち、いずれか一方を造粒して粒状物とする場合、該粒状物に、結合剤が配合されていることが好ましい。 In the preparation of the present invention, when any one of tranexamic acid or a salt thereof and ibuprofen is granulated to form a granular material, it is preferable that a binder is blended in the granular material.
すなわち、本発明においては、（１）トラネキサム酸またはその塩、ならびに結合剤を用いて造粒して得た粒状物、およびイブプロフェンを含有する製剤、（２）イブプロフェンならびに結合剤を用いて造粒して得られた粒状物、およびトラネキサム酸またはその塩を含有する製剤、（３）トラネキサム酸またはその塩、ならびに結合剤を用いて造粒して得た粒状物、およびイブプロフェンならびに結合剤を用いて造粒して得た粒状物を含有する製剤が好ましく、中でもトラネキサム酸またはその塩、ならびに結合剤を用いて造粒して得た粒状物、およびイブプロフェンならびに結合剤を用いて造粒して得た粒状物を含有する製剤であることがより好ましい。 That is, in the present invention, (1) a granule obtained by granulation using tranexamic acid or a salt thereof, and a binder, and a preparation containing ibuprofen, (2) granulation using ibuprofen and the binder And granules containing tranexamic acid or a salt thereof, (3) granules obtained by granulating using tranexamic acid or a salt thereof, and a binder, and using ibuprofen and a binder A preparation containing granulates obtained by granulation is preferable, among which granule obtained by granulation using tranexamic acid or a salt thereof, and a binder, and granulation using ibuprofen and a binder. A preparation containing the obtained granular material is more preferable.
特に本発明において、トラネキサム酸もしくはその塩、および／またはイブプロフェンを溶融造粒する場合、結合剤を加えて溶融することが好ましい。本発明において、溶融造粒を行なう際の加熱の温度は、配合される結合剤の融点よりも高く、かつ溶融造粒を行なうトラネキサム酸もしくはその塩、またはイブプロフェンの融点よりも低いことが好ましい。例えば、６５〜１００℃が好ましく、７５〜８５℃がより好ましい。 In particular, in the present invention, when tranexamic acid or a salt thereof and / or ibuprofen is melt-granulated, it is preferable to add a binder and melt it. In the present invention, the heating temperature for melt granulation is preferably higher than the melting point of the binder to be blended and lower than the melting point of tranexamic acid or a salt thereof or ibuprofen for melt granulation. For example, 65-100 degreeC is preferable and 75-85 degreeC is more preferable.
また、本発明にかかる結合剤の配合量は、トラネキサム酸もしくはその塩、またはイブプロフェンの配合量により調節されることが好ましい。例えば、トラネキサム酸またはその塩、および結合剤を配合する場合、トラネキサム酸またはその塩、および結合剤の配合比は、３０００：１〜１：７５が好ましく、７５０：１〜８：１５がより好ましい。また、イブプロフェンおよび結合剤を配合する場合、イブプロフェンおよび結合剤の配合比は、２０００：１〜１：２５が好ましく、６００：１〜２：５がより好ましい。 Moreover, it is preferable that the compounding quantity of the binder concerning this invention is adjusted with the compounding quantity of tranexamic acid or its salt, or ibuprofen. For example, when blending tranexamic acid or a salt thereof and a binder, the blending ratio of tranexamic acid or a salt thereof and the binder is preferably 3000: 1 to 1:75, and more preferably 750: 1 to 8:15. . Moreover, when mix | blending ibuprofen and a binder, 2000: 1 to 1:25 are preferable and, as for the compounding ratio of ibuprofen and a binder, 600: 1 to 2: 5 are more preferable.
さらに、本発明の製剤は、トラネキサム酸またはその塩、およびイブプロフェン以外の薬効成分を配合することができる。配合可能な成分としては、アスピリン、アスピリンアルミニウム、サザピリン、エテンザミド、サリチルアミド、アセトアミノフェン、イソプロピルアンチピリン等の解熱鎮痛薬、カフェイン、無水カフェイン、安息香酸ナトリウムカフェイン等の中枢神経興奮薬、ブロムワレリル尿素、アリルイソプロピルアセチル尿素等の鎮静剤、マレイン酸クロルフェニラミン、フマル酸クレマスチン、ジフェンヒドラミン、サリチル酸ジフェンヒドラミン、マレイン酸カルビノキサン、メキタジン、酒石酸アリメマジン、塩酸ジフェニルピラリン、塩酸トリプロリジン等の抗ヒスタミン薬、塩化リゾチーム、ブロメライン、セラペプターゼ、セミアルカリプロティナーゼ、グリチルリチン酸、グリチルリチン酸ジカリウム、グリチルリチン酸アンモニウム、グリチルレチン酸、アズレンスルホン酸ナトリウム等の抗炎症薬、リン酸ジヒドロコデイン、リン酸コデイン、塩酸ノスカピン、ノスカピン、臭化水素酸デキストロメトルファン、デキストロメトルファンフェノールフタリン塩、リン酸ジメモルファン、ヒベンズ酸チペピジン、クエン酸チペピジン、塩酸エプラジノン、メチルエフェドリン、塩酸メチルエフェドリン、塩酸メトキシフェナミン、塩酸トリメトキノール、塩酸フェニルプロパノールアミン等の鎮咳薬、塩酸Ｌ−エチルシステイン、グアヤコールスルホン酸カリウム、クレゾール酸カリウム、グアイフェネシン、塩酸ブロムヘキシン、カルボシステイン、塩酸アンブロキソール等の去痰薬、テオフィリン、アミノフィリン、ジプロフィリン等の気管支拡張薬、ベラドンナ（総）アルカロイド、ベラドンナエキス、ヨウ化イソプロパミド、臭化水素酸スコポラミン、ロートエキス、臭化ブチルスコポラミン、臭化メチルベナクチジウム、臭化チメピジウム、ピレンゼピン等の抗アセチルコリン剤、セチルピリジニウム、塩化セチルピリジニウム、ポピドンヨード、グルコン酸クロルヘキシジン、塩化ベンザルコニウム、塩化デカリニウム、チモール、ヨウ素・ヨウ化カリウム、フェノール、塩酸クロルヘキシジン、クレオソート、塩化ベンゼトニウム等の殺菌消毒剤、塩酸ジブカイン、アミノ安息香酸エチル、リドカイン、塩酸リドカイン、オキセサゼイン等の局所麻酔剤、ビタミンＡ、肝油、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、アスコルビン酸カルシウム、ビタミンＤ、ビタミンＥ、コハク酸トコフェロールカルシウム等のビタミン剤、パントテン酸、パンテノール、パントテン酸ナトリウム、パントテン酸カルシウム、パンテチン、ニコチン酸、ニコチン酸アミド、グルクロン酸、グルクロノラクトン、アミノエチルスルホン酸、ビオチン、γ−オリザノール等の代謝性成分、地竜、ケイヒ、ゴオウ、ショウキョウ、キキョウ、マオウ、カンゾウ、キョウニン、ハンゲ、シャゼンソウ、セネガ、サイコ、ブクリョウ、シンイ等の生薬およびこれら生薬の抽出物（エキス、チンキ等）等を挙げることができるが、上記のもののみに限定されるべきものではない。これらの医薬成分は、単一成分を配合してもよく、２つ以上のものを組み合わせて配合してもよい。 Furthermore, the formulation of this invention can mix | blend tranexamic acid or its salt, and medicinal ingredients other than ibuprofen. Components that can be combined include antipyretic analgesics such as aspirin, aspirin aluminum, sazapyrine, etenzamide, salicylamide, acetaminophen, isopropylantipyrine, central nervous stimulants such as caffeine, anhydrous caffeine, sodium benzoate caffeine, Sedatives such as bromovaleryl urea and allyl isopropyl acetyl urea, chlorpheniramine maleate, clemastine fumarate, diphenhydramine, diphenhydramine salicylate, carbinoxane maleate, mequitazine, alimemazine tartrate, diphenylpyralin hydrochloride, triprolidine hydrochloride, and other antihistamines Lysozyme, bromelain, serrapeptase, semi-alkaline proteinase, glycyrrhizic acid, dipotassium glycyrrhizinate, ammonium glycyrrhizinate , Anti-inflammatory drugs such as glycyrrhetinic acid, sodium azulenesulfonate, dihydrocodeine phosphate, codeine phosphate, noscapine hydrochloride, noscapine, dextromethorphan hydrobromide, dextromethorphan phenolphthalein salt, dimemorphan phosphate, hibenzic acid Antitussives such as tipepidine, tipepidine citrate, epradinone hydrochloride, methylephedrine, methylephedrine hydrochloride, methoxyphenamine hydrochloride, trimethquinol hydrochloride, phenylpropanolamine hydrochloride, L-ethylcysteine hydrochloride, potassium guaiacol sulfonate, potassium cresolate, Expectorants such as guaifenesin, bromhexine hydrochloride, carbocysteine, ambroxol hydrochloride, bronchodilators such as theophylline, aminophylline, diprofylline, belladonna Total) Alkaloids, belladonna extract, isopropamide iodide, scopolamine hydrobromide, funnel extract, butyl scopolamine bromide, methylbenactidium bromide, thimepidium bromide, pirenzepine and other antiacetylcholine agents, cetylpyridinium, cetylpyridinium chloride, Disinfectants such as popidone iodine, chlorhexidine gluconate, benzalkonium chloride, decalinium chloride, thymol, iodine / potassium iodide, phenol, chlorhexidine hydrochloride, creosote, benzethonium chloride, dibucaine hydrochloride, ethyl aminobenzoate, lidocaine, lidocaine hydrochloride , local anesthetics such as oxethazaine, vitamin a, cod liver oil, vitamin B 1, vitamin B 2, vitamin B 6, vitamin B 12, vitamin C, calcium ascorbate, vitamin D, vitamin E, vitamins such as tocopherol calcium succinate, pantothenic acid, panthenol, sodium pantothenate, calcium pantothenate, panthetin, nicotinic acid, nicotinamide, glucuronic acid, glucuronolactone, aminoethylsulfonic acid, biotin , Gamma-oryzanol and other metabolic components, earth dragons, keihi, gooh, shokyo, kyoukyo, maou, licorice, kyounin, hange, shazenso, senega, psycho, bukkyou, shinyi and extracts of these herbal medicines (extracts) , Tincture, and the like), but should not be limited to the above. These pharmaceutical ingredients may be blended with a single ingredient or in combination of two or more.
本発明の製剤の製造にあたっては、前記の混合、造粒、圧縮成型、コーティングのほかに、必要に応じて、さらに粉砕、混合、造粒、加熱、乾燥等の工程を製造工程に含めることができる。 In the production of the preparation of the present invention, in addition to the mixing, granulation, compression molding, and coating, the production process may further include pulverization, mixing, granulation, heating, drying, and the like as necessary. it can.
また、本発明の製剤においては、前記結合剤の他に、さらに必要に応じて適当な添加物を加えることができる。添加物は、本発明の効果を損なわない範囲で適宜加えればよい。
添加物としては、賦形剤、崩壊剤、滑沢剤、コーティング剤等を挙げることができる。 賦形剤としては、例えば、結晶セルロース、粉末セルロース、バレイショデンプン、軽質無水ケイ酸、含水二酸化ケイ素、二酸化ケイ素、沈降炭酸カルシウム、無水リン酸水素カルシウム、酸化マグネシウム、乳酸カルシウム、ケイ酸カルシウム、メタケイ酸アルミン酸マグネシウム、合成ヒドロタルサイト、合成ケイ酸アルミニウム、乳糖、白糖、Ｄ−マンニトール、エリスリトール、ブドウ糖、果糖等を挙げることができる。
Moreover, in the formulation of this invention, a suitable additive can be further added as needed other than the said binder. Additives may be appropriately added within a range not impairing the effects of the present invention.
Examples of the additive include an excipient, a disintegrant, a lubricant, and a coating agent. Examples of excipients include crystalline cellulose, powdered cellulose, potato starch, light anhydrous silicic acid, hydrous silicon dioxide, silicon dioxide, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, magnesium oxide, calcium lactate, calcium silicate, and metasilica. Examples thereof include magnesium aluminate, synthetic hydrotalcite, synthetic aluminum silicate, lactose, sucrose, D-mannitol, erythritol, glucose, fructose and the like.
崩壊剤としては、例えば、カルメロース、カルメロースカルシウム、クロスカルメロースナトリウム、低置換度ヒドロキシプロピルセルロース、クロスポビドン、アルギン酸、部分アルファー化デンプン、ベントナイト等を挙げることができる。
滑沢剤としては、例えば、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク、ショ糖脂肪酸エステル、グリセリン脂肪酸エステル、ポリエチレングリコール、硬化油等を挙げることができる。
コーティング剤としては、例えば、アミノアルキルメタクリレートコポリマー、アラビアゴム、エチルセルロース、カルナウバロウ、カルボキシビニルポリマー、ステアリン酸マグネシウム、セラック、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、プルラン、ポビドン、ポリビニルアルコール、マクロゴール等を挙げることができる。
これら添加物は、前記に挙げたものに限定されるものではなく、また、これらのうち１種を用いてもよいし、２種以上を組み合わせて用いてもよい。
Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropylcellulose, crospovidone, alginic acid, partially pregelatinized starch, and bentonite.
Examples of the lubricant include magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, glycerin fatty acid ester, polyethylene glycol, and hardened oil.
Examples of the coating agent include aminoalkyl methacrylate copolymer, gum arabic, ethyl cellulose, carnauba wax, carboxyvinyl polymer, magnesium stearate, shellac, hydroxypropylcellulose, hydroxypropylmethylcellulose, pullulan, povidone, polyvinyl alcohol, macrogol and the like. Can do.
These additives are not limited to those mentioned above, and one kind of them may be used, or two or more kinds may be used in combination.
本発明の製剤におけるトラネキサム酸またはその塩、およびイブプロフェンの配合比は、適宜決めることができるが、トラネキサム酸またはその塩、およびイブプロフェンの配合比は、１００：１〜１：２００が好ましく、２：３〜５：２がより好ましい。 The mixing ratio of tranexamic acid or a salt thereof and ibuprofen in the preparation of the present invention can be determined as appropriate, but the mixing ratio of tranexamic acid or a salt thereof and ibuprofen is preferably 100: 1 to 1: 200, 2: 3-5: 2 is more preferable.
さらに、本発明の製剤の患者への投与量は、患者の性別、年齢、体重、症状、投与方法、投与回数、投与時期等により適宜検討を行ない、適当な投与量を決めればよい。例えば、経口投与の場合、トラネキサム酸またはその塩については、トラネキサム酸として１日あたり１０〜３０００ｍｇ投与することが好ましく、４００〜７５０ｍｇ投与することがより好ましく、７５０ｍｇ投与することが特に好ましい。イブプロフェンについては、イブプロフェンとして１日あたり３０〜２０００ｍｇ投与することが好ましく、３００〜６００ｍｇ投与することがより好ましく、４５０ｍｇ投与することが特に好ましい。 Furthermore, the dosage of the preparation of the present invention to a patient may be determined appropriately by appropriately examining the patient's sex, age, weight, symptoms, administration method, frequency of administration, administration timing, and the like. For example, in the case of oral administration, tranexamic acid or a salt thereof is preferably administered as tranexamic acid in an amount of 10 to 3000 mg per day, more preferably 400 to 750 mg, and particularly preferably 750 mg. About ibuprofen, it is preferable to administer 30-2000 mg per day as ibuprofen, It is more preferable to administer 300-600 mg, It is especially preferable to administer 450 mg.
すなわち、トラネキサム酸またはその塩、およびイブプロフェンを含有する製剤として、その配合量は、１日あたりトラネキサム酸またはその塩をトラネキサム酸として１０〜３０００ｍｇ、イブプロフェンを３０〜２０００ｍｇ投与（服用）することになるように配合したものが好ましく、１日あたりトラネキサム酸またはその塩をトラネキサム酸として４００〜７５０ｍｇ、イブプロフェンを３００〜６００ｍｇ投与（服用）することになるように配合したものがより好ましく、１日あたりトラネキサム酸またその塩をトラネキサム酸として７５０ｍｇ、イブプロフェンを４５０ｍｇ投与（服用）することになるように配合したものが特に好ましい。 That is, as a preparation containing tranexamic acid or a salt thereof and ibuprofen, the compounding amount is 10 to 3000 mg of tranexamic acid or a salt thereof as tranexamic acid and 30 to 2000 mg of ibuprofen per day. It is preferable to mix 400-750 mg of tranexamic acid or a salt thereof as tranexamic acid and 300-600 mg of ibuprofen (take), and more preferable to be tranexam per day. It is particularly preferable that 750 mg of acid or its salt as tranexamic acid and 450 mg of ibuprofen be administered (taken).
本発明の製剤は、炎症の予防および／または治療用、解熱鎮痛用、感冒薬の製剤として用いられるのが好ましい。 The preparation of the present invention is preferably used as a preparation for prevention and / or treatment of inflammation, antipyretic analgesia, and cold medicine.
以下に、実施例を示して本発明を説明するが、本発明はこれらにのみ限定されるべきものではない。 Hereinafter, the present invention will be described with reference to examples. However, the present invention should not be limited to these examples.
（実施例１）
表１の実施例１に記載のイブプロフェンおよびマクロゴール６０００を６５℃水浴上のガラスビーカー中にて攪拌し、次いで冷却し、１８メッシュの篩にて整粒し、造粒物を得た。得られた造粒物にトラネキサム酸および乳糖を加えて混合し、ハンドプレスにて打錠し、実施例１の錠剤（直径８．５ｍｍ、重量２５０ｍｇ）を得た。
Example 1
Ibuprofen and Macrogol 6000 described in Example 1 of Table 1 were stirred in a glass beaker on a 65 ° C. water bath, then cooled, and sized with an 18 mesh sieve to obtain a granulated product. Tranexamic acid and lactose were added to the granulated product, mixed, and tableted with a hand press to obtain the tablet of Example 1 (diameter 8.5 mm, weight 250 mg).
（実施例２）
表１の実施例２に記載のイブプロフェンおよび硬化油を６５℃水浴上のガラスビーカー中にて攪拌し、次いで冷却し、１８メッシュの篩にて整粒し、造粒物を得た。得られた造粒物にトラネキサム酸および乳糖を加えて混合し、ハンドプレスにて打錠し、実施例２の錠剤（直径８．５ｍｍ、重量２５０ｍｇ）を得た。
(Example 2)
The ibuprofen and hardened oil described in Example 2 in Table 1 were stirred in a glass beaker on a 65 ° C. water bath, then cooled, and sized with an 18 mesh sieve to obtain a granulated product. Tranexamic acid and lactose were added to the granulated product, mixed, and tableted with a hand press to obtain the tablet of Example 2 (diameter 8.5 mm, weight 250 mg).
（実施例３）
表１の実施例３に記載のトラネキサム酸およびマクロゴール６０００を６５℃水浴上のガラスビーカー中にて攪拌し、次いで冷却し、１８メッシュの篩にて整粒し、造粒物を得た。得られた造粒物にイブプロフェンおよび乳糖を加えて混合し、ハンドプレスにて打錠し、実施例３の錠剤（直径８．５ｍｍ、重量２５０ｍｇ）を得た。
(Example 3)
Tranexamic acid and Macrogol 6000 described in Example 3 in Table 1 were stirred in a glass beaker on a 65 ° C. water bath, then cooled, and sized with an 18 mesh sieve to obtain a granulated product. Ibuprofen and lactose were added to the granulated product, mixed, and tableted with a hand press to obtain the tablet of Example 3 (diameter 8.5 mm, weight 250 mg).
（実施例４）
表１の実施例４に記載のトラネキサム酸および硬化油を６５℃水浴上のガラスビーカー中にて攪拌し、次いで冷却し、１８メッシュの篩にて整粒し、造粒物を得た。得られた造粒物にイブプロフェンおよび乳糖を加えて混合し、ハンドプレスにて打錠し、実施例４の錠剤（直径８．５ｍｍ、重量２５０ｍｇ）を得た。
Example 4
The tranexamic acid and hydrogenated oil described in Example 4 in Table 1 were stirred in a glass beaker on a 65 ° C. water bath, then cooled, and sized with an 18 mesh sieve to obtain a granulated product. Ibuprofen and lactose were added to the granulated product, mixed, and tableted with a hand press to obtain the tablet of Example 4 (diameter 8.5 mm, weight 250 mg).
（比較例１）
表１の比較例１に記載のトラネキサム酸、イブプロフェンおよび乳糖を混合し、ハンドプレスにて打錠し、比較例１の錠剤（直径８．５ｍｍ、重量２５０ｍｇ）を得た。
(Comparative Example 1)
Tranexamic acid, ibuprofen and lactose described in Comparative Example 1 in Table 1 were mixed and compressed by hand press to obtain the tablet of Comparative Example 1 (diameter 8.5 mm, weight 250 mg).
（試験例１）
実施例１〜４および比較例１の錠剤を５０℃にて各々瓶密栓保存し、製造直後の錠剤の体積および１０日後の錠剤の体積を測定し、さらに下記の式にしたがって膨張比を算出した。結果を表２に示す。
(Test Example 1)
The tablets of Examples 1 to 4 and Comparative Example 1 were each sealed in a bottle at 50 ° C., the volume of the tablet immediately after production and the volume of the tablet after 10 days were measured, and the expansion ratio was calculated according to the following formula. . The results are shown in Table 2.
体積膨張比（％）＝｛（１０日後の錠剤の体積）−（製造直後の錠剤の体積）｝／（製造直後の錠剤の体積）×１００ Volume expansion ratio (%) = {(volume of the tablet after 10 days) − (volume of the tablet immediately after production)} / (volume of the tablet immediately after production) × 100
表２の結果に示すとおり、トラネキサム酸およびイブプロフェンを実質的に互いに接触しないように配合した錠剤は、体積が膨張しないことがわかった。したがって、トラネキサム酸およびイブプロフェンを含有する錠剤を製造する際には、トラネキサム酸およびイブプロフェンを実質的に互いに接触しないように配合させることにより、体積が膨張せず、錠剤の割れも生じない錠剤を製造することができることがわかった。 As shown in the results of Table 2, it was found that tablets formulated with tranexamic acid and ibuprofen so as not to substantially contact each other did not expand in volume. Therefore, when manufacturing tablets containing tranexamic acid and ibuprofen, the tablets are produced so that the volume does not expand and the tablet does not crack by blending tranexamic acid and ibuprofen so as not to contact each other substantially. I found out that I can do it.
本発明によれば、トラネキサム酸またはその塩、およびイブプロフェンを含有する安定した製剤およびその製造方法を提供することができる。具体的には、トラネキサム酸またはその塩、およびイブプロフェンを含有する医薬用製剤、特に解熱鎮痛剤および感冒薬の製剤を安定に保存することができ、有用なものである。 ADVANTAGE OF THE INVENTION According to this invention, the stable formulation containing tranexamic acid or its salt, and ibuprofen, and its manufacturing method can be provided. Specifically, pharmaceutical preparations containing tranexamic acid or a salt thereof and ibuprofen, particularly antipyretic analgesics and cold medicine preparations, can be stably stored and are useful.
Claims (17)
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| JP2007061435A JP5465824B2 (en) | 2006-03-24 | 2007-03-12 | Pharmaceutical preparation and method for producing the same |
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