JP2010111666A - Pharmaceutical composition for antitussive and/or expectorant use containing cetirizine - Google Patents
Pharmaceutical composition for antitussive and/or expectorant use containing cetirizine Download PDFInfo
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Abstract
Description
本発明は、セチリジンを含有する気道杯細胞過形成抑制剤ひいては鎮咳及び／又は去痰のための医薬組成物に関する。 The present invention relates to a pharmaceutical composition for airway goblet cell hyperplasia containing cetirizine, and thus for coughing and / or expectoration.
正常な気道の表面の多くは線毛上皮細胞で被われており、その中に気道粘液を産生する杯細胞が散在し、気道分泌液と線毛との協調作用により異物を排除している。しかし、気道分泌が亢進すると、気道内にそれらが貯留して細菌増殖の温床となるため、気道感染を反復したり気道閉塞をきたしたりすることが知られている。また、喫煙、種々の大気汚染物質又はアレルゲンの吸入、気道感染等で、気道分泌亢進のみならず杯細胞の過形成等が惹起され、これが長引くと急性呼吸器疾患から慢性難治性呼吸器疾患へ移行してしまう恐れがある（以上、例えば、非特許文献１参照）。このような悪循環を防ぐためには、急性期における通常の去痰剤による治療のみならず杯細胞過形成を抑制するための対処も併せて必要である。 Many of the normal airway surfaces are covered with ciliated epithelial cells, interspersed with goblet cells that produce airway mucus, and exclude foreign substances by the cooperative action of airway secretions and cilia. However, it is known that when airway secretion increases, they accumulate in the airway and become a hotbed for bacterial growth, causing repeated airway infection and airway obstruction. In addition, cigarette smoking, inhalation of various air pollutants or allergens, respiratory tract infection, etc. cause not only increased airway secretion but also hyperplasia of goblet cells, etc. If prolonged, this changes from acute respiratory disease to chronic intractable respiratory disease There is a risk of migration (see, for example, Non-Patent Document 1). In order to prevent such a vicious cycle, not only treatment with a normal expectorant in the acute phase but also a countermeasure for suppressing goblet cell hyperplasia is necessary.
抗アレルギー剤の１種であるセチリジン塩酸塩（塩酸セチリジン）は、（ア）ヒスタミンＨ１受容体拮抗作用、（イ）好酸球の遊走抑制および活性化抑制作用、（ウ）メディエータ遊離抑制作用、等の作用を有し、本邦では、アレルギー性鼻炎、蕁麻疹、湿疹・皮膚炎、痒疹、皮膚掻痒症の効能・効果が認められている（例えば、非特許文献２参照）。しかし、感冒薬として処方又は利用されることは承認効能の面から、現状では考え難いものがある。 Cetirizine hydrochloride (cetirizine hydrochloride), which is one of the antiallergic agents, has (a) histamine H1 receptor antagonism, (b) eosinophil migration inhibition and activation inhibition, (c) mediator release inhibition, In Japan, the efficacy and effects of allergic rhinitis, urticaria, eczema / dermatitis, urticaria and cutaneous pruritus are recognized in Japan (for example, see Non-Patent Document 2). However, it is difficult to prescribe or use as a cold medicine from the viewpoint of approval efficacy.
一方、セチリジンを含有する感冒関連医薬組成物として、以下のものがこれまでに開示されているが、これらはあくまでも感冒時における鼻水・鼻閉等の鼻炎症状を抑える技術の開示に過ぎないものと言える。
（１）抗コリン薬のベラドンナ総アルカロイドによる鼻汁抑制作用が、セチリジン塩酸塩の併用により増強することが開示されている（特許文献１〜２参照）。
（２）交感神経刺興奮薬のエフェドリン類による卵白アルブミン感作モルモットの鼻呼吸抵抗の低下作用が、セチリジン塩酸塩の併用により増強することが見出された。これにより、鼻閉改善に優れた効果があることが判明し、感冒や鼻炎等に伴う鼻閉改善に優れることが記載されている（特許文献３参照）。また、セチリジンとプソイドエフェドリンとを分けて存在させたアレルギー疾患用錠剤が開示されている（特許文献４〜５参照）。
（３）有効成分として、イブプロフェン又はアセトアミノフェンから選ばれる解熱鎮痛剤、セチリジン、エバスチン、フェキソフェナジン及びロラタジンから選ばれる抗アレルギー剤、鎮咳剤、去痰剤、喀痰溶解剤、交感神経興奮剤及び中枢神経興奮剤から選ばれる薬剤を含有する感冒薬カプセル剤が開示されている（特許文献６参照）。
On the other hand, the cold related pharmaceutical compositions containing cetirizine have been disclosed so far, but these are merely disclosures of techniques for suppressing nasal inflammation such as runny nose and nasal congestion at the time of cold. I can say that.
(1) It is disclosed that the nasal secretion suppression action by the belladonna total alkaloid of an anticholinergic agent is enhanced by the combined use of cetirizine hydrochloride (see Patent Documents 1 and 2).
(2) It has been found that the effect of reducing nasal respiratory resistance of ovalbumin-sensitized guinea pigs by the sympathomimetic ephedrines is enhanced by the combined use of cetirizine hydrochloride. Thus, it has been found that there is an excellent effect in improving nasal congestion, and it is described that it is excellent in improving nasal congestion associated with colds and rhinitis (see Patent Document 3). In addition, tablets for allergic diseases in which cetirizine and pseudoephedrine are separately present are disclosed (see Patent Documents 4 to 5).
(3) Antipyretic analgesic selected from ibuprofen or acetaminophen as an active ingredient, antiallergic agent selected from cetirizine, ebastine, fexofenadine and loratadine, antitussive, expectorant, sputum solubilizer, sympathomimetic and central A cold medicine capsule containing a drug selected from nerve stimulants has been disclosed (see Patent Document 6).
また、これまでにアゼラスチン、メキタジン、ケトチフェン及びクレマスチンに気道杯細胞過形成抑制作用を有することが本発明者によって開示されている（特許文献７参照）が、その他の抗ヒスタミン剤及び抗アレルギー剤については不明である。 Further, it has been disclosed by the present inventors that azelastine, mequitazine, ketotifen and clemastine have an airway goblet cell hyperplasia inhibitory effect (see Patent Document 7), but other antihistamines and antiallergic agents are unknown. It is.
優れた気道杯細胞過形成抑制作用を有する新規な医薬組成物を見出すことが本発明の課題である。これまでに、当該分野における研究は十分になされてきたとはいえず、本発明の成果により、新規な予防又は治療効果を有する医薬組成物が提供できるものと考えられる。特に本発明は、呼吸器疾患等の予防又は治療、更には感冒等の予防又は治療に役立つと考えられる。 It is an object of the present invention to find a novel pharmaceutical composition having an excellent inhibitory effect on airway goblet cell hyperplasia. Until now, it cannot be said that the research in the said field | area was fully done, and it is thought that the pharmaceutical composition which has a novel preventive or therapeutic effect can be provided by the result of this invention. In particular, the present invention is considered to be useful for the prevention or treatment of respiratory diseases and the like, and further the prevention or treatment of colds and the like.
本発明者は、気道杯細胞過形成抑制作用を有する医薬組成物について長年にわたり鋭意研究を行っているが、今回の研究では、先に開示したアゼラスチン、メキタジン、ケトチフェン及びクレマスチン以外の抗ヒスタミン剤および抗アレルギー剤についても気道杯細胞に対する作用を調べた。その結果、特定の抗アレルギー剤にのみ気道杯細胞過形成抑制作用が発現し、抗アレルギー剤によっては逆に増悪させるものも存在するという意外な事実を新たに見出し、本発明を完成するに至った。 The present inventor has conducted extensive research on pharmaceutical compositions having an inhibitory effect on airway goblet cell hyperplasia for many years. In this study, antihistamines and antiallergies other than azelastine, mequitazine, ketotifen and clemastine disclosed above were studied. The effect of the agent on airway goblet cells was also examined. As a result, the present inventors completed the present invention by newly finding the surprising fact that only certain anti-allergic agents exhibit an inhibitory effect on airway goblet cell hyperplasia and some anti-allergic agents exacerbate them. It was.
すなわち本発明は、
１．セチリジン又はその塩を含有する気道杯細胞過形成抑制剤、
２．１に記載の気道杯細胞過形成抑制剤を含有する鎮咳及び／又は去痰のための医薬組成物、
３．感冒の治療に用いるための２に記載の医薬組成物、
４．急性又は慢性気管支炎の治療に用いるための２に記載の医薬組成物、
５．慢性気道疾患における急性呼吸器感染時の症状の治療に用いるための２に記載の医薬組成物、
である。
That is, the present invention
1. Airway goblet cell hyperplasia inhibitor containing cetirizine or a salt thereof,
A pharmaceutical composition for antitussive and / or expectorant, comprising the airway goblet cell hyperplasia inhibitor according to 2.1,
3. 2. A pharmaceutical composition according to 2, for use in the treatment of colds,
4). 2. The pharmaceutical composition according to 2, for use in the treatment of acute or chronic bronchitis,
5). 2. The pharmaceutical composition according to 2, for use in the treatment of symptoms during acute respiratory infection in chronic airway disease,
It is.
本発明におけるセチリジンとは、化学名が、２−[２−[４−[（ＲＳ）−（４−クロロフェニル）フェニルメチル]−１−ピペラジン−１−イル]エトキシ]酢酸であり、公知の化合物である。セチリジンの塩としては、医薬上容認される塩であれば、特に限定されないが、セチリジンの塩としては、セチリジン塩酸塩（以下、塩酸セチリジンとも称す）が好ましい。 Cetirizine in the present invention is a known compound having a chemical name of 2- [2- [4-[(RS)-(4-chlorophenyl) phenylmethyl] -1-piperazin-1-yl] ethoxy] acetic acid. It is. The cetirizine salt is not particularly limited as long as it is a pharmaceutically acceptable salt, but the cetirizine salt is preferably cetirizine hydrochloride (hereinafter also referred to as cetirizine hydrochloride).
本発明の「慢性気道疾患」とは、例えば、慢性閉塞性肺疾患（ＣＯＰＤ）、気管支拡張症、気管支喘息、肺結核、塵肺症、肺気腫、びまん性汎気管支炎等が挙げられる。 Examples of the “chronic airway disease” of the present invention include chronic obstructive pulmonary disease (COPD), bronchiectasis, bronchial asthma, pulmonary tuberculosis, pneumoconiosis, pulmonary emphysema, diffuse panbronchitis and the like.
本発明における、「治療する」とは、病気又は症状を治癒させること又は改善させること或いは症状を抑制させることを意味する。 In the present invention, “treat” means to cure or ameliorate a disease or symptom or to suppress a symptom.
本発明のセチリジン又はその塩を含有する医薬組成物は、気道杯細胞の過形成を顕著に抑制し、ひいては優れた鎮咳及び／又は去痰作用を有することから有用である。 The pharmaceutical composition containing cetirizine or a salt thereof of the present invention is useful because it significantly suppresses hyperplasia of airway goblet cells, and thus has excellent antitussive and / or expectorant action.
本発明のセチリジン又はその塩を含有する医薬組成物は、一般に考えられる感冒等の症状の治療又は予防に有用であるが、好適には、急性又は慢性気管支炎等の症状の治療又は予防に有用であり、更に好適には、急性呼吸器感染症患者における急性気管支炎等の症状又はＣＯＰＤ、気管支拡張症、気管支喘息、肺結核、塵肺症、肺気腫、びまん性汎気管支炎等の慢性気道疾患を有する患者における急性気管支炎等の症状の治療又は予防にも有用である。 The pharmaceutical composition containing cetirizine or a salt thereof of the present invention is useful for the treatment or prevention of symptoms such as common cold, but is preferably useful for the treatment or prevention of symptoms such as acute or chronic bronchitis. More preferably, it has symptoms such as acute bronchitis in patients with acute respiratory infection or chronic airway diseases such as COPD, bronchiectasis, bronchial asthma, pulmonary tuberculosis, pneumoconiosis, emphysema, diffuse panbronchitis, etc. It is also useful for the treatment or prevention of symptoms such as acute bronchitis in patients.
本発明に用いられる、セチリジン塩酸塩（塩酸セチリジン）は第１５改正日本薬局方第１追補２００８に収載され、医療用医薬品として市販されている。 Cetirizine hydrochloride (cetirizine hydrochloride) used in the present invention is listed in the 15th revised Japanese Pharmacopoeia First Supplement 2008 and is marketed as a prescription drug.
セチリジン塩酸塩の１回投与量は、適応症や年齢により異なるが、通常、５ｍｇ〜４０ｍｇであり、これを１日に、１〜３回投与する。 The single dose of cetirizine hydrochloride varies depending on the indication and age, but is usually 5 mg to 40 mg, and this is administered 1 to 3 times a day.
本発明の医薬組成物の剤形が固形製剤の場合において、セチリジン塩酸塩の含有量は、通常、２ｍｇ〜５０ｍｇであり、好適には、５ｍｇ〜３０ｍｇである。 When the dosage form of the pharmaceutical composition of the present invention is a solid preparation, the content of cetirizine hydrochloride is usually 2 mg to 50 mg, preferably 5 mg to 30 mg.
本発明の医薬組成物の剤形が液剤の場合において、セチリジン塩酸塩の含有量は通常、０．５ｍｇ／ｍＬ〜４０ｍｇ／ｍＬであり、好適には、１ｍｇ／ｍＬ〜１０ｍｇ／ｍＬである。 When the dosage form of the pharmaceutical composition of the present invention is a liquid, the content of cetirizine hydrochloride is usually 0.5 mg / mL to 40 mg / mL, preferably 1 mg / mL to 10 mg / mL.
本発明においては、上記有効成分の他、必要に応じて解熱鎮痛消炎薬、その他の鎮咳薬、その他の去痰薬、交感神経興奮薬、中枢神経興奮薬、消炎酵素類、ビタミン類、生薬類等を本発明の効果を損なわない範囲で含有させることができる。 In the present invention, in addition to the above active ingredients, antipyretic analgesic / anti-inflammatory drugs, other antitussives, other expectorants, sympathomimetic drugs, central nervous stimulants, anti-inflammatory enzymes, vitamins, herbal medicines, etc. Can be contained within a range not impairing the effects of the present invention.
これらの具体的な剤形としては、例えば、錠剤、細粒剤（顆粒剤、散剤を含む）、カプセル、液剤（シロップ剤を含む）等をあげることができ、各剤形に適した添加剤や基剤を適宜使用し、日本薬局方等に記載された通常の方法に従い、製造することができる。 Specific examples of these dosage forms include tablets, fine granules (including granules and powders), capsules, liquids (including syrups) and the like, and additives suitable for each dosage form. Can be produced according to the usual methods described in the Japanese Pharmacopoeia.
上記各剤形において、その剤形に応じ、通常使用される各種添加剤を使用することもできる。例えば、賦形剤、安定化剤、コーティング剤、滑沢剤、吸着剤、結合剤、崩壊剤、界面活性剤、着色剤、ｐＨ調節剤及び香料等を添加することができる。 In the above dosage forms, various commonly used additives can be used depending on the dosage form. For example, an excipient, a stabilizer, a coating agent, a lubricant, an adsorbent, a binder, a disintegrant, a surfactant, a colorant, a pH adjuster, and a fragrance can be added.
以下に、実施例及び試験例を示し、本発明をさらに詳細に説明するが、本発明の範囲はこれらに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but the scope of the present invention is not limited thereto.
（実施例１）錠剤
（１）成分
（表１）
１錠中 （ｍｇ）
−−−−−−−−−−−−−−−−−−−−−
セチリジン塩酸塩 １０
乳糖 ７０
ステアリン酸マグネシウム ８
ヒドロキシプロピルセルロース ２５
トウモロコシデンプン 適量
−−−−−−−−−−−−−−−−−−−−−。
(Example 1) Tablet (1) Component (Table 1)
In 1 tablet (mg)
---------------------
Cetirizine hydrochloride 10
Lactose 70
Magnesium stearate 8
Hydroxypropylcellulose 25
Corn starch adequate amount ---------------------.
（２）製法
上記成分及び分量をとり、日局製剤総則「錠剤」の項に準じて錠剤を製造する。
(2) Manufacturing method Take the above ingredients and the amount, and manufacture tablets according to the section of “General Tablets” “Tablet”.
（実施例２）顆粒剤
（１）成分
（表２）
１包中 （ｍｇ）
−−−−−−−−−−−−−−−−−−−−−
セチリジン塩酸塩 １０
乳糖 ３００
ポリビニルピロリドン ２５
トウモロコシデンプン 適量
−−−−−−−−−−−−−−−−−−−−−。
(Example 2) Granules (1) Ingredients (Table 2)
In 1 packet (mg)
---------------------
Cetirizine hydrochloride 10
Lactose 300
Polyvinylpyrrolidone 25
Corn starch adequate amount ---------------------.
（２）製法
上記成分及び分量をとり、日局製剤総則「顆粒剤」の項に準じて細粒剤を製造する。
(2) Production method Take the above ingredients and quantities, and produce a fine granule according to the section of the Japanese Pharmacopoeia General Rules “Granule”.
（実施例３）カプセル剤
（１）成分
（表３）
１〜２カプセル中 （ｍｇ）
−−−−−−−−−−−−−−−−−−−−−
セチリジン塩酸塩 １０
乳糖 １５０
ポリビニルピロリドン ２５
トウモロコシデンプン 適量
−−−−−−−−−−−−−−−−−−−−−。
(Example 3) Capsule (1) Component (Table 3)
In 1-2 capsules (mg)
---------------------
Cetirizine hydrochloride 10
Lactose 150
Polyvinylpyrrolidone 25
Corn starch adequate amount ---------------------.
（２）製法
上記成分及び分量をとり、日局製剤総則「顆粒剤」の項に準じて細粒剤を製造した後、カプセルに充てんして硬カプセル剤を製造する。
(2) Manufacturing method After taking the above components and quantities and preparing a fine granule according to the section of the Japanese Pharmacopoeia General Rules “Granules”, it is filled into capsules to produce hard capsules.
（実施例４）シロップ剤
（１）成分
（表４）
１０ｍＬ中 （ｍｇ）
−−−−−−−−−−−−−−−−−−−−−
セチリジン塩酸塩 １０
安息香酸ナトリウム ７０
グリセリン １００
ポリビニルアルコール ８０
白糖 １２００
精製水 残部
−−−−−−−−−−−−−−−−−−−−−。
Example 4 Syrup (1) Ingredient (Table 4)
In 10 mL (mg)
---------------------
Cetirizine hydrochloride 10
Sodium benzoate 70
Glycerin 100
Polyvinyl alcohol 80
Sucrose 1200
Purified water balance ---------------------.
（２）製法
上記成分及び分量をとり、日局製剤総則「シロップ剤」の項に準じてシロップ剤を製造した後、褐色ガラス瓶に充てんしてシロップ剤を製造する。
(2) Manufacturing method Take the above ingredients and quantities, and manufacture a syrup according to the Japanese general formulation “Syrup” section, then fill it into a brown glass bottle to manufacture a syrup.
（試験例）杯細胞形成抑制効果試験
（１）被験物質
抗アレルギー剤の、ペミロラストカリウムは三菱ウエルファーマ製造の商品名アレギサール（登録商標）１０ｍｇ錠を、アンレキサノクスは武田薬品工業製造の商品名ソルファ（登録商標）５０ｍｇ錠を乳鉢で微細化して使用し、セチリジン塩酸塩はＳＩＧＭＡ社製のものを使用した。
(Test example) Goblet cell formation inhibitory effect test (1) Test substance Anti-allergic agent, pemirolast potassium is a brand name of Aregisal (registered trademark) 10 mg tablet manufactured by Mitsubishi Pharma, Anlexanox is a brand name of Takeda Pharmaceutical Solfa (registered trademark) 50 mg tablets were refined in a mortar, and cetirizine hydrochloride manufactured by SIGMA was used.
各被験物質は投与液量が５ｍＬ／Ｋｇになるように、試験当日に０．５％カルボキシメチルセルロース（ＣＭＣ）液を加えて調製した。 Each test substance was prepared by adding a 0.5% carboxymethylcellulose (CMC) solution on the test day so that the dose amount was 5 mL / Kg.
（２）動物
Ｆ３４４／ＤｕＣｒｊ雄性ラットの１０週齢を日本チャールズリバー（株）から購入し、温度２０〜２６℃、湿度３０〜７０％、照明時間７時〜１９時に制御されたラット飼育室内でラット用ブラケットテーパーケージに５匹ずつ入れ、飼料（マウス・ラット飼育用Ｆ−２、船橋農場製）および水フィルターを通した水道水を自由に摂取させて約１週間予備飼育した。試験開始日に肉眼で動物の健康状態を観察し良好なことを確認して体重を測定し無作為に１群７匹に群分けして用いた。
(2) Animal F344 / DuCrj male rat 10-week-old was purchased from Charles River Japan Co., Ltd. in a rat breeding room controlled at a temperature of 20 to 26 ° C., a humidity of 30 to 70%, and a lighting time of 7:00 to 19:00. Five rats were placed in a rat bracket taper cage, and the animals were preliminarily raised for about one week by freely ingesting feed (F-2 for breeding mice and rats, manufactured by Funabashi Farm) and tap water through a water filter. On the day of the test, the health condition of the animal was observed with the naked eye to confirm that it was good, the body weight was measured, and the animals were randomly divided into 7 groups per group.
（３）気道粘膜障害モデルの作製方法
ラットにペントバルビタール５０ｍｇ／Ｋｇを腹腔内投与して麻酔をかけ、仰臥位に固定し、頚部喉頭側皮膚を正中に切開して、筋肉を鈍性に分離し気管を露出させた。口腔からラット用の液体気管内投与器具を用いて、気管露出部から確認しながら気管内に挿入し、１％リポポリサッカライド（ＬＰＳ）溶液を０．１ｍＬ投与した。直ちに、気管周囲筋肉を縫合して切開部皮膚をアロンアルファ（登録商標）で接着させて気道粘膜障害動物を作成した。
(3) Preparation method of airway mucosal injury model Rats are anesthetized by intraperitoneal administration of pentobarbital 50mg / Kg, fixed in the supine position, the skin of the cervical larynx is incised in the midline, and the muscles are bluntly separated The trachea was exposed. Using a liquid endotracheal administration device for rats from the oral cavity, it was inserted into the trachea while confirming from the exposed part of the trachea, and 0.1 mL of 1% lipopolysaccharide (LPS) solution was administered. Immediately, the peritracheal muscle was sutured, and the skin of the incision was adhered with Aron Alpha (registered trademark) to create an airway mucosal disorder animal.
（４）試験
試験開始日の午前中に被験物質（対象群にはＣＭＣ液）を経口投与した後に、上述の方法でＬＰＳ溶液を気管内投与し、その日の夕刻に再度被験物質（対象群にはＣＭＣ液）を経口投与した。２日目と３日目は１日２回（午前と夕刻）被験物質（対象群にはＣＭＣ液）を経口投与した。
(4) Test After the test substance (CMC solution for the subject group) was orally administered in the morning of the test start day, the LPS solution was intratracheally administered by the above-mentioned method, and again in the evening of the day, the test substance (to the subject group). Was administered orally. On the second and third days, the test substance (CMC solution in the subject group) was orally administered twice a day (morning and evening).
４日目に体重を測定した後、ペントバルビタール麻酔下で頚動脈を切断して放血安楽死させてから、喉頭蓋部より肺までの気管を採取し、生理食塩水で洗浄後、１０％中性緩衝ホルマリン液に浸漬し充分に固定した。 After measuring body weight on the 4th day, the carotid artery was amputated under pentobarbital anesthesia and exsanguinated, and the trachea from the epiglottis to the lungs was collected, washed with physiological saline, and 10% neutral buffered It was immersed in formalin solution and fixed sufficiently.
充分に固定後、気管を左右主気管支分岐部より上部約１０ｍｍで横断し、さらに上方に６ｍｍ以上の長さで横断し、管状の気管を切り出し観察材料とした。 After sufficiently fixing, the trachea was traversed about 10 mm above the left and right main bronchial bifurcations, and further traversed at a length of 6 mm or more, and the tubular trachea was cut out and used as an observation material.
常法により、管状の気管を縦断して短冊状の薄切気管標本を作製し、これをアルシアン青・ＰＡＳ染色で染色後、６ｍｍ長の範囲内の杯細胞数を顕微鏡下で計測した。なお、１例について２本の短冊状気管組織標本の杯細胞合計数を計測数とした。 By a conventional method, a tubular trachea was longitudinally cut to prepare a strip-like thin cut trachea specimen, which was stained with Alcian blue / PAS stain, and then the number of goblet cells within a range of 6 mm length was measured under a microscope. In addition, the total number of goblet cells of two strip-shaped tracheal tissue specimens for one example was used as the measurement number.
杯細胞形成抑制率（％）を次式より求めた。 Goblet cell formation inhibition rate (%) was calculated from the following formula.
（式１）
杯細胞形成抑制率（％）＝［１−Ｂ／Ａ］×１００
Ａ：ＣＭＣ投与群の杯細胞数の平均値
Ｂ：被験物質投与群の杯細胞数の平均値
(Formula 1)
Goblet cell formation inhibition rate (%) = [1-B / A] × 100
A: Average value of the number of goblet cells in the CMC administration group B: Average value of the number of goblet cells in the test substance administration group
（５）試験結果
得られた杯細胞形成抑制率の結果を表５に示す。なお、各値とも１群７匹の平均値である。
(5) Test results Table 5 shows the results of the goblet cell formation inhibition rate obtained. Each value is an average value of 7 animals per group.
（表５）
被験物質（投与量：ｍｇ／Ｋｇ／回） 杯細胞形成抑制率（％）
−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−
ペミロラストカリウム（１） −２７．１
アンレキサノクス（１０） ０．９
セチリジン塩酸塩（１．５） １３．６
−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−。
(Table 5)
Test substance (dose: mg / Kg / time) Goblet cell formation inhibition rate (%)
--------------------------------
Pemirolast potassium (1) -27.1
Anlexanox (10) 0.9
Cetirizine hydrochloride (1.5) 13.6
--------------------------------.
表５より、同じ抗アレルギー剤でも杯細胞過形成を増悪させるもの、効果の発現がないもの、抑制効果を有するものが存在し、セチリジンは気道杯細胞形成抑制効果を有することが判明した。 From Table 5, it was found that some of the same anti-allergic agents exacerbate goblet cell hyperplasia, no effect, and no inhibitory effect, and cetirizine has an inhibitory effect on airway goblet cell formation.
本発明のセチリジン又はその塩を含有する医薬組成物は、気道杯細胞の過形成を抑制し、ひいては優れた鎮咳及び／又は去痰作用を有することから有用である。 The pharmaceutical composition containing cetirizine or a salt thereof of the present invention is useful because it suppresses hyperplasia of airway goblet cells and thus has an excellent antitussive and / or expectorant action.
本発明のセチリジン又はその塩を含有する医薬組成物は、一般に考えられる感冒等の症状の治療又は予防に有用であるが、好適には、急性又は慢性気管支炎等の症状の治療又は予防に有用であり、更に好適には、急性呼吸器感染症患者における急性気管支炎等の症状又はＣＯＰＤ、気管支拡張症、気管支喘息、肺結核、塵肺症、肺気腫、びまん性汎気管支炎等の慢性気道疾患を有する患者における急性気管支炎等の症状の治療又は予防にも有用である。
The pharmaceutical composition containing cetirizine or a salt thereof of the present invention is useful for the treatment or prevention of symptoms such as common cold, but is preferably useful for the treatment or prevention of symptoms such as acute or chronic bronchitis. More preferably, it has symptoms such as acute bronchitis in patients with acute respiratory infection or chronic airway diseases such as COPD, bronchiectasis, bronchial asthma, pulmonary tuberculosis, pneumoconiosis, emphysema, diffuse panbronchitis, etc. It is also useful for the treatment or prevention of symptoms such as acute bronchitis in patients.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2002255816A (en) * | 2001-03-05 | 2002-09-11 | Taisho Pharmaceut Co Ltd | Composition for treating cold |
| JP2002348240A (en) * | 2001-05-25 | 2002-12-04 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
| JP2008143807A (en) * | 2006-12-07 | 2008-06-26 | Sato Pharmaceutical Co Ltd | Capsule of drug for common cold and method for producing the same |
| JP2008169193A (en) * | 2006-04-27 | 2008-07-24 | Daiichi Sankyo Healthcare Co Ltd | Antihistamine-containing pharmaceutical composition for suppressing goblet cell hyperplasia |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2002255816A (en) * | 2001-03-05 | 2002-09-11 | Taisho Pharmaceut Co Ltd | Composition for treating cold |
| JP2002348240A (en) * | 2001-05-25 | 2002-12-04 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
| JP2008169193A (en) * | 2006-04-27 | 2008-07-24 | Daiichi Sankyo Healthcare Co Ltd | Antihistamine-containing pharmaceutical composition for suppressing goblet cell hyperplasia |
| JP2008143807A (en) * | 2006-12-07 | 2008-06-26 | Sato Pharmaceutical Co Ltd | Capsule of drug for common cold and method for producing the same |
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